Skip to main content

Advertisement

SpringerLink
Log in

Evodiamine as an anticancer agent: a comprehensive review on its therapeutic application, pharmacokinetic, toxicity, and metabolism in various cancers

  • Review
  • Published:
Cell Biology and Toxicology Aims and scope Submit manuscript

Abstract

Evodiamine is a major alkaloid component found in the fruit of Evodia rutaecarpa. It shows the anti-proliferative potential against a wide range of cancers by suppressing cell growth, invasion, and metastasis and inducing apoptosis both in vitro and in vivo. Evodiamine shows its anticancer potential by modulating aberrant signaling pathways. Additionally, the review focuses on several therapeutic implications of evodiamine, such as epigenetic modification, cancer stem cells, and epithelial to mesenchymal transition. Moreover, combinatory drug therapeutics along with evodiamine enhances the anticancer efficacy of chemotherapeutic drugs in various cancers by overcoming the chemo resistance and radio resistance shown by cancer cells. It has been widely used in preclinical trials in animal models, exhibiting very negligible side effects against normal cells and effective against cancer cells. The pharmacokinetic and pharmacodynamics-based collaborations of evodiamine are also included. Due to its poor bioavailability, synthetic analogs of evodiamine and its nano capsule have been formulated to enhance its bioavailability and reduce toxicity. In addition, this review summarizes the ongoing research on the mechanisms behind the antitumor potential of evodiamine, which proposes an exciting future for such interests in cancer biology.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

Not applicable.

Abbreviations

ROS:

Reactive oxygen species

Top I:

Topoisomerase I

CSC:

Cancer stem cell

EMT:

Epithelial to mesenchymal transition

DR:

Death receptor

Akt:

Protein kinase B

NF-κB:

Nuclear factor kappa-light-chain-enhancer of activated B

SHH:

Sonic Hedgehog

GLI1:

GLI family zinc finger 1

cdk:

Cyclin-dependent kinase

p:

Phosphorylated

chk:

Checkpoint kinase

DNMT:

DNA methyl transferase

Notch3:

Neurogenic locus notch homolog protein 3

mTOR:

Mammalian target of rapamycin

S6K1:

Ribosomal protein S6 kinase beta-1

Mcl-1:

Myeloid cell leukemia 1

PARP :

Poly ADP ribose polymerase

Nbk:

Natural born killer

ER:

Estrogen receptor

MEK:

Mitogen-activated protein kinase kinase

ERK:

Extracellular-signal-regulated kinase

PPAR:

Peroxisome proliferator-activated receptor gamma

STAT3:

Signal transducer and activator of transcription 3

SHP-1:

Src homology 2 domain-containing protein tyrosine phosphatase 1

WWOX:

WWdomain-containing oxidoreductase

VEGF:

Vascular endothelial growth factor

NOD1:

Nucleotide-binding oligomerization domain-containing protein 1

MAPK:

Mitogen-activated protein kinase

YAP:

Yes-associated protein

JNK:

C-Jun N-terminal kinase

JAK2:

Janus Kinase 2

MMP:

Matrix metallopeptidase

Her-2:

Human epidermal growth factor receptor 2

PLK1:

Polo-like kinase 1

Wnt:

Wingless-related integration site

IL:

Interleukin

PERK:

Protein kinase R-like endoplasmic reticulum kinase

PI3K:

Phosphatidylinositol 3-kinase

NO:

Nitric oxide

Mcl-1:

Myeloid cell leukemia 1

SIRT1:

Sirtuin

PKB:

Protein kinase B

TGFβ:

Transforming growth factor beta

Smad2:

Mothers against decapentaplegic homolog 2

GADD45:

Growth arrest and DNA damage-inducible 45

Mcm:

Minichromosome maintenance complex component

TRADD:

Tumor necrosis factor receptor type 1-associated DEATH domain

IRAK:

Interleukin-1 receptor-associated kinase

cyt-c:

Cytochrome-c

AIF:

Apoptosis-inducing factor

ENDOG:

Endonuclease G

c-Met:

Tyrosine-protein kinase Met

Src:

Sarcoma

Myt-1:

Myelin transcription factor 1

miR:

MicroRNA

NSCLC:

Non-small cell lung cancer

PRAME:

Preferentially expressed antigen of melanoma

HIF-1α:

Hypoxia-inducible factor 1-alpha

IGF-1:

Insulin-like growth factor

PTEN:

Phosphatase and tensin homolog

cAMP:

Cyclic adenosine monophosphate

TRAIL:

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand

uPA:

Urokinase-type plasminogen activator

COX-2:

Cyclooxygenase-2

ICAM-1:

Intercellular cell adhesion molecule-1

MDR:

Multidrug resistance

XIAP:

X-linked inhibitor of apoptosis protein

IAP:

Inhibitor of apoptosis protein

FLIP:

Fas‐associated death domain (FADD)‐like IL‐1β‐converting enzyme‐inhibitory protein

IkBα:

Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha

TNF:

Tumor necrosis factor

IKK:

IκB kinase

ABCG2:

ATP-binding cassette super-family G member 2

LPS:

Lipopolysaccharide

iNOS:

Inducible NOS

CCA:

Cholangiocarcinoma

PGI:

Phosphoglucose isomerase

AMF:

Autocrine motility factor

SHP:

Phosphatase shatterproof 1 N-terminal

NBD:

Nucleotide binding domain

HSP70:

Heat shock protein

Sox2:

Sex determining region Y)-box 2

KLF4:

Kruppel-like factor 4

Oct4:

Octamer-binding transcription factor 4

LRP5:

Low-density lipoprotein receptor-related protein 5

SCD1:

Stearoyl-CoA desaturase

HER:

Human epidermal growth factor receptor

hes-5:

Hes family BHLH transcription factor 5

Mst1/2:

Mammalian sterile 20-like kinase (MST) 1/2

MET:

Mesenchymal to epithelial transition

HGF:

Human growth factor

TGF-β:

Transforming growth factor beta

5-aza:

5-Azacytidine

TSA:

Trichostatin A

AMPK:

5′ Adenosine monophosphate-activated protein kinase

L-OHP:

Oxaliplatin

HCT-116/L-OHP:

L-OHP resistant HCT-116

CCRF-CEM/C1:

Camptothecin-resistant leukemic lymphoblast cells

A2780R2000 :

Camptothecin-resistant A2780

A2780/PTXR :

Paclitaxel resistant A2780

ZJW:

Zuo-Jin-Wan

5-FU:

5-Fluorouracil

Pt:

Platinum

ERCC1:

Excision repair cross-complementing 1

TS:

Thymidylate synthase

HDAC:

Histone deacetylase

H2AX:

H2A histone family member X

DOX:

Doxorubicin

LD50:

Lethal dose, 50%

IC50 :

Inhibitory concentration, 50%

T/NT ratio:

Tumor:nontumor ratio

SUV:

Standardized uptake value

AFP:

α-Fetoprotein

CRC:

Colorectal cancer

TSGF:

Tumor specific growth factor

NEEPN:

Evodiamine-phospholipid nano complex

MSNs:

Mesoporous silica nanoparticles

References

  • Bak E, et al. Inhibitory effect of evodiamine alone and in combination with rosiglitazone on in vitro adipocyte differentiation and in vivo obesity related to diabetes. Int J Obes. 2010;34(2):250–60.

    Article  CAS  Google Scholar 

  • Barrero MJ, Boué S, Belmonte JCI. Epigenetic mechanisms that regulate cell identity. Cell Stem Cell. 2010;7(5):565–70.

    Article  CAS  PubMed  Google Scholar 

  • Bhatia K, Das A. Combinatorial drug therapy in cancer-new insights. Life Sciences. 2020;118134.

  • Bukowski K, Kciuk M, Kontek R. Mechanisms of multidrug resistance in cancer chemotherapy. Int J Mol Sci. 2020;21(9):3233.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Burotto M, et al. The MAPK pathway across different malignancies: a new perspective. Cancer. 2014;120(22):3446–56.

    Article  CAS  PubMed  Google Scholar 

  • Cai Q, et al. Toxicity of Evodiae fructus on rat liver mitochondria: the role of oxidative stress and mitochondrial permeability transition. Molecules. 2014;19(12):21168–82.

    Article  PubMed  PubMed Central  Google Scholar 

  • Chan AL-F, et al. Evodiamine stabilizes topoisomerase I-DNA cleavable complex to inhibit topoisomerase I activity. Molecules. 2009;14(4):1342–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chandarlapaty S. Negative feedback and adaptive resistance to the targeted therapy of cancer. Cancer Discov. 2012;2(4):311–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chang W-L, et al. Tubulin-binding agents down-regulate matrix metalloproteinase-2 and-9 in human hormone-refractory prostate cancer cells–a critical role of cdk1 in mitotic entry. Biochem Pharmacol. 2015;94(1):12–21.

    Article  CAS  PubMed  Google Scholar 

  • Chen MC, et al. Anti-proliferative effects of evodiamine on human thyroid cancer cell line ARO. J Cell Biochem. 2010;110(6):1495–503.

    Article  CAS  PubMed  Google Scholar 

  • Chen T-C, et al. Evodiamine from Evodia rutaecarpa induces apoptosis via activation of JNK and PERK in human ovarian cancer cells. Phytomedicine. 2016;23(1):68–78.

    Article  CAS  PubMed  Google Scholar 

  • Cheng ZM, et al. Effects of evodiamine on invasion and polo-like kinase 1 expression of human gastric cancer cell [J]. J Jiangsu Univ (Medicine Edition) 2011;21:69–72.

  • Chien C-C, et al. Activation of JNK contributes to evodiamine-induced apoptosis and G 2/M arrest in human colorectal carcinoma cells: a structure-activity study of evodiamine. PLoS One. 2014;9(6):e99729.

    Article  PubMed  PubMed Central  Google Scholar 

  • Chou S-T, et al. Exploration of anti-cancer effects and mechanisms of Zuo-Jin-Wan and its alkaloid components in vitro and in orthotopic HepG2 xenograft immunocompetent mice. BMC Complement Altern Med. 2017;17(1):121.

    Article  PubMed  PubMed Central  Google Scholar 

  • Cohen SM, et al. Hepatotoxicity associated with the use of White Flood, a nutritional supplement. Pract Gastroenterol. 2012;36(10):45–7.

    Google Scholar 

  • Dong G, et al. Selection of evodiamine as a novel topoisomerase I inhibitor by structure-based virtual screening and hit optimization of evodiamine derivatives as antitumor agents. J Med Chem. 2010;53(21):7521–31.

    Article  CAS  PubMed  Google Scholar 

  • Dong G, et al. New tricks for an old natural product: discovery of highly potent evodiamine derivatives as novel antitumor agents by systemic structure–activity relationship analysis and biological evaluations. 2012;55(17):7593–613.

  • Du J, et al. Evodiamine induces apoptosis and inhibits metastasis in MDA-MB-231 human breast cancer cells in vitro and in vivo. Oncol Rep. 2013;30(2):685–94.

    Article  CAS  PubMed  Google Scholar 

  • Du J, et al. Berberine and evodiamine act synergistically against human breast cancer MCF-7 cells by inducing cell cycle arrest and apoptosis. Anticancer Res. 2017;37(11):6141–51.

    CAS  PubMed  Google Scholar 

  • Duchartre Y, Kim Y-M, Kahn M. The Wnt signaling pathway in cancer. Crit Rev Oncol Hematol. 2016;99:141–9.

    Article  PubMed  Google Scholar 

  • Ebi H. EGFR-Mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition. Ann Oncol. 2012;23:xi41.

    Article  Google Scholar 

  • Fang C, et al. Evodiamine induces G2/M arrest and apoptosis via mitochondrial and endoplasmic reticulum pathways in H446 and H1688 human small-cell lung cancer cells. PLoS One. 2014;9(12):e115204.

    Article  PubMed  PubMed Central  Google Scholar 

  • Fang Q, et al. Evodiamine selectively inhibits multiple myeloma cell growth by triggering activation of intrinsic apoptosis pathway. Onco Targets Ther. 2019;12:11383.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fendler A, et al. Inhibiting WNT and NOTCH in renal cancer stem cells and the implications for human patients. Nat Commun. 2020;11(1):1–16.

    Article  Google Scholar 

  • García-Gómez R, Bustelo XR, Crespo P. Protein–protein interactions: emerging oncotargets in the RAS-ERK pathway. Trends Cancer. 2018;4(9):616–33.

    Article  PubMed  Google Scholar 

  • Gu Y, Mohammad IS, Liu Z. Overview of the STAT-3 signaling pathway in cancer and the development of specific inhibitors. Oncol Lett. 2020;19(4):2585–94.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Guan X, et al. Combined effects of berberine and evodiamine on colorectal cancer cells and cardiomyocytes in vitro. Eur J Pharmacol 2020;173031.

  • Guo X-X, et al. Evodiamine induces apoptosis in SMMC-7721 and HepG2 cells by suppressing NOD1 signal pathway. Int J Mol Sci. 2018;19(11):3419.

    Article  PubMed  PubMed Central  Google Scholar 

  • Guo Q, et al. Evodiamine inactivates NF-κB and potentiates the antitumor effects of gemcitabine on tongue cancer both in vitro and in vivo. Onco Targets Ther. 2019;12:257.

    Article  CAS  PubMed  Google Scholar 

  • Guo YJ, et al. ERK/MAPK signalling pathway and tumorigenesis. Exp Ther Med. 2020;19(3):1997–2007.

    PubMed  PubMed Central  Google Scholar 

  • Gupta SC, et al. Inhibiting NF-κB activation by small molecules as a therapeutic strategy. Biochim Biophys Acta (BBA)-Gene Regul Mech. 2010;1799(10–12):775–87.

    Article  CAS  Google Scholar 

  • Han S, et al. Evodiamine selectively targets cancer stem-like cells through the p53–p21-Rb pathway. Biochem Biophys Res Commun. 2016;469(4):1153–8.

    Article  CAS  PubMed  Google Scholar 

  • He C, Wan H. Drug metabolism and metabolite safety assessment in drug discovery and development. Expert Opin Drug Metab Toxicol. 2018;14(10):1071–85.

    Article  CAS  PubMed  Google Scholar 

  • Heo SK, et al. Evodiamine and rutaecarpine inhibit migration by LIGHT via suppression of NADPH oxidase activation. J Cell Biochem. 2009;107(1):123–33.

    Article  CAS  PubMed  Google Scholar 

  • Hong Z, et al. Effects of evodiamine on PI3K/Akt and MAPK/ERK signaling pathways in pancreatic cancer cells. Int J Oncol. 2020;56(3):783–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hu J, et al. Improved absorption and in vivo kinetic characteristics of nanoemulsions containing evodiamine–phospholipid nanocomplex. Int J Nanomed. 2014;9:4411.

    Google Scholar 

  • Hu C, et al. Evodiamine sensitizes BGC-823 gastric cancer cells to radiotherapy in vitro and in vivo. Mol Med Rep. 2016;14(1):413–9.

    Article  CAS  PubMed  Google Scholar 

  • Hu C-Y, et al. Evodiamine exerts an anti-hepatocellular carcinoma activity through a WWOX-dependent pathway. Molecules. 2017;22(7):1175.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hu X, et al. Antiproliferative effects of alkaloid evodiamine and its derivatives. Int J Mol Sci. 2018;19(11):3403.

    Article  PubMed  PubMed Central  Google Scholar 

  • Huang Y-C, Guh J-H, Teng C-M. Induction of mitotic arrest and apoptosis by evodiamine in human leukemic T-lymphocytes. Life Sci. 2004;75(1):35–49.

    Article  CAS  PubMed  Google Scholar 

  • Huang J, et al. Antiproliferation effect of evodiamine in human colon cancer cells is associated with IGF-1/HIF-1α downregulation. Oncol Rep. 2015;34(6):3203–11.

    Article  CAS  PubMed  Google Scholar 

  • Huang C, et al. Effect of evodiamine and berberine on the interaction between DNMTs and target microRNAs during malignant transformation of the colon by TGF-β1. Oncol Rep. 2017;37(3):1637–45.

    Article  CAS  PubMed  Google Scholar 

  • Hung P-H, et al. Inhibitory effect of evodiamine on aldosterone release by Zona glomerulosa cells in male rats. Chin J Physiol. 2001;44(2):53–8.

    CAS  PubMed  Google Scholar 

  • Hwang ST, et al. Evodiamine mitigates cellular growth and promotes apoptosis by targeting the c-met pathway in prostate cancer cells. Molecules. 2020;25(6):1320.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hyun SY, et al. Evodiamine inhibits both stem cell and non-stem-cell populations in human cancer cells by targeting heat shock protein 70. Theranostics. 2021;11(6):2932.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jia J, et al. Inhibition of human liver cancer cell growth by evodiamine involves apoptosis and deactivation of PI3K/AKT pathway. Appl Biol Chem. 2020;63(1):1–8.

    Article  Google Scholar 

  • Jiang J, Hu C. Evodiamine: a novel anti-cancer alkaloid from Evodia rutaecarpa. Molecules. 2009;14(5):1852–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jin W. Role of JAK/STAT3 signaling in the regulation of metastasis, the transition of cancer stem cells, and chemoresistance of cancer by epithelial–mesenchymal transition. Cells. 2020;9(1):217.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jin J, et al. Identification of genetic mutations in cancer: challenge and opportunity in the new era of targeted therapy. Front Oncol. 2019;9:263.

    Article  PubMed  PubMed Central  Google Scholar 

  • Junlin L, et al. The effects of evodiamine on autophagy in human colon adenocarcinoma lovo cells. Chin J Gen Surg. 2011;26(1):41–4.

    Google Scholar 

  • Kabacaoglu D, et al. NF-κB/Rel transcription factors in pancreatic cancer: focusing on RelA, c-Rel, and RelB. Cancers. 2019;11(7):937.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kan SF, et al. Inhibitory effects of evodiamine on the growth of human prostate cancer cell line LNCaP. Int J Cancer. 2004;110(5):641–51.

    Article  CAS  PubMed  Google Scholar 

  • Kan SF, et al. Anti-proliferative effects of evodiamine on human prostate cancer cell lines DU145 and PC3. J Cell Biochem. 2007;101(1):44–56.

    Article  CAS  PubMed  Google Scholar 

  • Khan M, et al. Evodiamine sensitizes U87 glioblastoma cells to TRAIL via the death receptor pathway. Mol Med Rep. 2015;11(1):257–62.

    Article  CAS  PubMed  Google Scholar 

  • Kharkar PS. Cancer stem cell (CSC) inhibitors: a review of recent patents (2012–2015). Expert Opin Ther Pat. 2017;27(7):753–61.

    Article  CAS  PubMed  Google Scholar 

  • Kim H-J, et al. Effect of herbal Ephedra sinica and Evodia rutaecarpa on body composition and resting metabolic rate: a randomized, double-blind clinical trial in Korean premenopausal women. J Acupunct Meridian Stud. 2008;1(2):128–38.

    Article  PubMed  Google Scholar 

  • Kim SH, et al. Evodiamine suppresses survival, proliferation, migration and epithelial–mesenchymal transition of thyroid carcinoma cells. Anticancer Res. 2018;38(11):6339–52.

    Article  CAS  PubMed  Google Scholar 

  • Kim H, et al. Evodiamine eliminates colon cancer stem cells via suppressing Notch and Wnt signaling. Molecules. 2019a;24(24):4520.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim SH, et al. Evodiamine in combination with histone deacetylase inhibitors has synergistic cytotoxicity in thyroid carcinoma cells. Endocrine. 2019b;65(1):110–20.

    Article  CAS  PubMed  Google Scholar 

  • Komatsu K-I, Wakame K, Kano Y. Pharmacological properties of galenical preparation. XVI. Pharmacokinetics of evodiamine and the metabolite in rats. Biol Pharm Bull. 1993;16(9):935–8.

    Article  CAS  PubMed  Google Scholar 

  • Lee T-J, et al. Caspase-dependent and caspase-independent apoptosis induced by evodiamine in human leukemic U937 cells. Mol Cancer Ther. 2006;5(9):2398–407.

    Article  CAS  PubMed  Google Scholar 

  • Lee Y-C, et al. Targeting of topoisomerase I for prognoses and therapeutics of camptothecin-resistant ovarian cancer. PLoS One. 2015;10(7):e0132579.

    Article  PubMed  PubMed Central  Google Scholar 

  • Li L, et al. Microbial metabolism of evodiamine by Penicillium janthinellum and its application for metabolite identification in rat urine. Enzyme Microb Technol. 2006;39(4):561–7. https://doi.org/10.1016/j.enzmictec.2005.10.029.

    Article  CAS  Google Scholar 

  • Li HL, et al. MAPK pathways are involved in the inhibitory effect of berberine hydrochloride on gastric cancer MGC 803 cell proliferation and IL-8 secretion in vitro and in vivo. Mol Med Rep. 2016a;14(2):1430–8.

    Article  CAS  PubMed  Google Scholar 

  • Li Y-L, et al. Evodiamine induces apoptosis and enhances apoptotic effects of erlotinib in wild-type EGFR NSCLC cells via S6K1-mediated Mcl-1 inhibition. Med Oncol. 2016b;33(2):16.

    Article  PubMed  Google Scholar 

  • Li Y-L, et al. Evodiamine induces apoptosis and promotes hepatocellular carcinoma cell death induced by vorinostat via downregulating HIF-1α under hypoxia. Biochem Biophys Res Commun. 2018;498(3):481–6.

    Article  CAS  PubMed  Google Scholar 

  • Li C, et al. Development of EGFR-targeted evodiamine nanoparticles for the treatment of colorectal cancer. Biomater Sci. 2019;7(9):3627–39.

    Article  CAS  PubMed  Google Scholar 

  • Li FS, et al. BMP9 mediates the anticancer activity of evodiamine through HIF-1α/p53 in human colon cancer cells. Oncol Rep. 2020;43(2):415–26.

    CAS  PubMed  Google Scholar 

  • Liao C-H, et al. Antitumor mechanism of evodiamine, a constituent from Chinese herb Evodiae fructus, in human multiple-drug resistant breast cancer NCI/ADR-RES cells in vitro and in vivo. Carcinogenesis. 2005;26(5):968–75.

    Article  CAS  PubMed  Google Scholar 

  • Liao J-F, et al. Anti-inflammatory and anti-infectious effects of Evodia rutaecarpa (Wuzhuyu) and its major bioactive components. Chin Med. 2011;6(1):6.

    Article  PubMed  PubMed Central  Google Scholar 

  • Lijuan W, et al. Evodiamine induces extrinsic and intrinsic apoptosis of ovarian cancer cells via the mitogen-activated protein kinase/phosphatidylinositol-3-kinase/protein kinase B signaling pathways. J Tradit Chin Med. 2016;36(3):353–9.

    Article  Google Scholar 

  • Lin C, et al. Simultaneous determination of evodiamine and rutecarpine in rabbit plasma by LC-ESI-MS and its application to pharmacokinetics. Die Pharmazie-an Int J Pharm Sci. 2011;66(12):920–3.

    CAS  Google Scholar 

  • Lin L, et al. Effect of evodiamine on the proliferation and apoptosis of A549 human lung cancer cells. Mol Med Rep. 2016;14(3):2832–8.

    Article  CAS  PubMed  Google Scholar 

  • Lin H, et al. Development and in-vitro evaluation of co-loaded berberine chloride and evodiamine ethosomes for treatment of melanoma. Int J Pharm 2020;119278.

  • Liu A-J, et al. Evodiamine, a plant alkaloid, induces calcium/JNK-mediated autophagy and calcium/mitochondria-mediated apoptosis in human glioblastoma cells. Chem Biol Interact. 2013;205(1):20–8.

    Article  CAS  PubMed  Google Scholar 

  • Liu H, et al. Effect of evodiamine and berberine on miR-429 as an oncogene in human colorectal cancer. Onco Targets Ther. 2016;9:4121.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Luo C, et al. Research progress on evodiamine, a bioactive alkaloid of Evodiae fructus: focus on its anti-cancer activity and bioavailability. Exp Ther Med. 2021;22(5):1–11.

    Article  Google Scholar 

  • Meng Z-J, et al. Evodiamine inhibits the proliferation of human osteosarcoma cells by blocking PI3K/Akt signaling. Oncol Rep. 2015;34(3):1388–96.

    Article  CAS  PubMed  Google Scholar 

  • Mohan V, Agarwal R, Singh RP. A novel alkaloid, evodiamine causes nuclear localization of cytochrome-c and induces apoptosis independent of p53 in human lung cancer cells. Biochem Biophys Res Commun. 2016;477(4):1065–71.

    Article  CAS  PubMed  Google Scholar 

  • Mondal S, et al. Natural products: promising resources for cancer drug discovery. Anti-Cancer Agents Med Chem (Formerly Curr Med Chem-Anti-Cancer Agents). 2012;12(1):49–75.

    CAS  Google Scholar 

  • Morgensztern D, McLeod HL. PI3K/Akt/mTOR pathway as a target for cancer therapy. Anticancer Drugs. 2005;16(8):797–803.

    Article  CAS  PubMed  Google Scholar 

  • Morrison R, et al. Targeting the mechanisms of resistance to chemotherapy and radiotherapy with the cancer stem cell hypothesis. J Oncol 2011;2011

  • Myung JK, et al. Bioavailability enhancing activities of natural compounds from medicinal plants. J Med Plants Res. 2009;3(13):1204–11.

    Google Scholar 

  • Noorolyai S, et al. The relation between PI3K/AKT signalling pathway and cancer. Gene. 2019;698:120–8.

    Article  CAS  PubMed  Google Scholar 

  • Ogasawara M, Suzuki H. Inhibition by evodiamine of hepatocyte growth factor-induced invasion and migration of tumor cells. Biol Pharm Bull. 2004;27(4):578–82.

    Article  CAS  PubMed  Google Scholar 

  • Ogasawara M, Matsubara T, Suzuki H. Inhibitory effects of evodiamine on in vitro invasion and experimental lung metastasis of murine colon cancer cells. Biol Pharm Bull. 2001;24(8):917–20.

    Article  CAS  PubMed  Google Scholar 

  • O’Shea JJ, et al. The JAK-STAT pathway: impact on human disease and therapeutic intervention. Annu Rev Med. 2015;66:311–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oun R, Moussa YE, Wheate NJ. The side effects of platinum-based chemotherapy drugs: a review for chemists. Dalton Trans. 2018;47(19):6645–53.

    Article  CAS  PubMed  Google Scholar 

  • Pan X, et al. Evodiamine, a dual catalytic inhibitor of type I and II topoisomerases, exhibits enhanced inhibition against camptothecin resistant cells. Phytomedicine. 2012;19(7):618–24.

    Article  CAS  PubMed  Google Scholar 

  • Panda M, Biswal BK. Cell signaling and cancer: a mechanistic insight into drug resistance. Mol Biol Rep. 2019;46(5):5645–59.

    Article  CAS  PubMed  Google Scholar 

  • Panda M, Biswal BK. Evodiamine inhibits stemness and metastasis by altering the SOX9–β‐catenin axis in non‐small‐cell lung cancer. J Cell Biochem. 2022.

  • Panda M, Tripathi SK, Biswal BK. Plumbagin promotes mitochondrial mediated apoptosis in gefitinib sensitive and resistant A549 lung cancer cell line through enhancing reactive oxygen species generation. Mol Biol Rep. 2020;47:4155–68.

    Article  CAS  PubMed  Google Scholar 

  • Panda M, Tripathi SK, Biswal BK. SOX9: an emerging driving factor from cancer progression to drug resistance. Biochim Biophys Acta (BBA)-Rev Cancer. 2021;188517.

  • Pastushenko I, Blanpain C. EMT transition states during tumor progression and metastasis. Trends Cell Biol. 2019;29(3):212–26.

    Article  CAS  PubMed  Google Scholar 

  • Patel M, et al. NF-κB pathways in the development and progression of colorectal cancer. Transl Res. 2018;197:43–56.

    Article  CAS  PubMed  Google Scholar 

  • Peng X, et al. Evodiamine inhibits the migration and invasion of nasopharyngeal carcinoma cells in vitro via repressing MMP-2 expression. Cancer Chemother Pharmacol. 2015;76(6):1173–84.

    Article  CAS  PubMed  Google Scholar 

  • Qi W, Zhou Y, Fan Y. Effects of evodiamine on invasion and proliferation in human gastric cancer cell. Shandong Med J. 2010;34:016.

    Google Scholar 

  • Qiu C, et al. A promising antitumor activity of evodiamine incorporated in hydroxypropyl-β-cyclodextrin: pro-apoptotic activity in human hepatoma HepG2 cells. Chem Cent J. 2016;10(1):1–11.

    Article  Google Scholar 

  • Ramli S, et al. Long noncoding RNA UCA1 in gastrointestinal cancers: molecular regulatory roles and patterns, mechanisms, and interactions. J Oncol. 2021;2021.

  • Sachita K, et al. In vitro assessment of the anticancer potential of evodiamine in human oral cancer cell lines. Phytother Res. 2015;29(8):1145–51.

    Article  CAS  PubMed  Google Scholar 

  • Schnekenburger M, Dicato M, Diederich MF. Anticancer potential of naturally occurring immunoepigenetic modulators: a promising avenue? Cancer. 2019;125(10):1612–28.

    Article  CAS  PubMed  Google Scholar 

  • Seshacharyulu P, et al. Targeting the EGFR signaling pathway in cancer therapy. Expert Opin Ther Targets. 2012;16(1):15–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shakil MS, et al. In vivo toxicity studies of chitosan-coated cobalt ferrite nanocomplex for its application as MRI contrast dye. 2020;3(11):7952-7964.

  • Sharma S, Kelly TK, Jones PA. Epigenetics in cancer. Carcinogenesis. 2010;31(1):27–36.

    Article  CAS  PubMed  Google Scholar 

  • Shen H, et al. Evodiamine inhibits proliferation and induces apoptosis in gastric cancer cells. Oncol Lett. 2015;10(1):367–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sheng C, Miao Z, Zhang WJSINPC. Topoisomerase I inhibitors derived from natural products: structure–activity relationships and antitumor potency. Stud Nat Prod Chem. 2016;47:1–28.

    Article  CAS  Google Scholar 

  • Shi H-L, et al. Berberine counteracts enhanced IL-8 expression of AGS cells induced by evodiamine. Life Sci. 2013;93(22):830–9.

    Article  CAS  PubMed  Google Scholar 

  • Shi L, et al. Evodiamine exerts anti-tumor effects against hepatocellular carcinoma through inhibiting β-catenin-mediated angiogenesis. Tumor Biology. 2016;37(9):12791–803.

    Article  CAS  PubMed  Google Scholar 

  • Shi C-S, et al. Evodiamine induces cell growth arrest, apoptosis and suppresses tumorigenesis in human urothelial cell carcinoma cells. Anticancer Res. 2017a;37(3):1149–59.

    Article  CAS  PubMed  Google Scholar 

  • Shi PX, et al. Evodiamine suppresses proliferation of colon cancer HCT-116 cells in mice. Basic Clin Med. 2017b;37(10):1373–7.

    Google Scholar 

  • Shyr M-H, et al. Determination and pharmacokinetics of evodiamine in the plasma and feces of conscious rats. Anal Chim Acta. 2006;558(1–2):16–21.

    Article  CAS  Google Scholar 

  • Singh A, Settleman J. EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene. 2010;29(34):4741–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Siveen KS, et al. Targeting the STAT3 signaling pathway in cancer: role of synthetic and natural inhibitors. Biochim Biophys Acta (BBA)-Rev Cancer. 2014;1845(2):136–54.

    Article  CAS  Google Scholar 

  • Su T, et al. Evodiamine, a novel NOTCH3 methylation stimulator, significantly suppresses lung carcinogenesis in vitro and in vivo. Front Pharmacol. 2018;9:434.

    Article  PubMed  PubMed Central  Google Scholar 

  • Sui H, et al. Evodiamine suppresses ABCG2 mediated drug resistance by inhibiting p50/p65 NF-κB pathway in colorectal cancer. J Cell Biochem. 2016;117(6):1471–81.

    Article  CAS  PubMed  Google Scholar 

  • Sun HZ, et al. Investigation of the in vitro metabolism of evodiamine: characterization of metabolites and involved cytochrome p450 isoforms. Phytother Res. 2013;27(5):705–12. https://doi.org/10.1002/ptr.4766.

    Article  CAS  PubMed  Google Scholar 

  • Sun C, et al. Evodiamine inhibits the proliferation of leukemia cell line K562 by regulating peroxisome proliferators-activated receptor gamma (PPAR γ) pathway. J Recept Signal Transduction. 2016;36(4):422–8.

    Article  CAS  Google Scholar 

  • Takada Y, Kobayashi Y, Aggarwal BB. Evodiamine abolishes constitutive and inducible NF-κB activation by inhibiting IκBα kinase activation, thereby suppressing NF-κB-regulated antiapoptotic and metastatic gene expression, up-regulating apoptosis, and inhibiting invasion. J Biol Chem. 2005;280(17):17203–12.

    Article  CAS  PubMed  Google Scholar 

  • Takebe N, Nguyen D, Yang SX. Targeting notch signaling pathway in cancer: clinical development advances and challenges. Pharmacol Ther. 2014;141(2):140–9.

    Article  CAS  PubMed  Google Scholar 

  • Takebe N, et al. Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: clinical update. Nat Rev Clin Oncol. 2015;12(8):445.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tan Q, et al. Design and evaluation of a novel evodiamine-phospholipid complex for improved oral bioavailability. AAPS PharmSciTech. 2012;13(2):534–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tan Q, Zhang J. Evodiamine and its role in chronic diseases. Drug Discov Mother Nat 2016;315–328.

  • Tanabe S, et al. Interplay of EMT and CSC in cancer and the potential therapeutic strategies. Front Pharmacol. 2020;11:904.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Teschke R. Traditional Chinese Medicine induced liver injury. J Clin Transl Hepatol. 2014;2(2):80.

    PubMed  PubMed Central  Google Scholar 

  • Thu KL, et al. Genetic disruption of KEAP1/CUL3 E3 ubiquitin ligase complex components is a key mechanism of NF-kappaB pathway activation in lung cancer. J Thorac Oncol. 2011;6(9):1521–9.

    Article  PubMed  PubMed Central  Google Scholar 

  • Tripathi SK, Biswal BK. Piperlongumine, a potent anticancer phytotherapeutic: Perspectives on contemporary status and future possibilities as an anticancer agent. Pharmacol Res. 2020;156:104772.

    Article  CAS  PubMed  Google Scholar 

  • Tripathi SK, Panda M, Biswal BK. Emerging role of plumbagin: cytotoxic potential and pharmaceutical relevance towards cancer therapy. Food Chem Toxicol. 2019;125:566–82.

    Article  CAS  PubMed  Google Scholar 

  • Tripathi SK, et al. Recent updates on the resistance mechanisms to epidermal growth factor receptor tyrosine kinase inhibitors and resistance reversion strategies in lung cancer. Med Res Rev. 2020;40(6):2132–76.

    Article  CAS  PubMed  Google Scholar 

  • Tu Y-J, et al. Evodiamine activates autophagy as a cytoprotective response in murine Lewis lung carcinoma cells. Oncol Rep. 2013;29(2):481–90.

    Article  CAS  PubMed  Google Scholar 

  • Tune BXJ, et al. Matrix metalloproteinases in chemoresistance: regulatory roles, molecular interactions, and potential inhibitors. J Oncol. 2022;2022.

  • Wang C, et al. Effect of protein kinase C on human melanoma A375–S2 cell death induced by evodiamine. Yao Xue Xue Bao= Acta Pharmaceutica Sinica. 2005;40(11):1033–6.

    CAS  PubMed  Google Scholar 

  • Wang C, et al. Roles of SIRT1 and phosphoinositide 3-OH kinase/protein kinase C pathways in evodiamine-induced human melanoma A375–S2 cell death. J Pharmacol Sci. 2005a;97(4):494–500.

    Article  CAS  PubMed  Google Scholar 

  • Wang C, et al. Evodiamine induced human melanoma A375–S2 cell death partially through interleukin 1 mediated pathway. Biol Pharm Bull. 2005b;28(6):984–9.

    Article  CAS  PubMed  Google Scholar 

  • Wang X-N, et al. Enhancement of apoptosis of human hepatocellular carcinoma SMMC-7721 cells through synergy of berberine and evodiamine. Phytomedicine. 2008;15(12):1062–8.

    Article  CAS  PubMed  Google Scholar 

  • Wang C, Li S, Wang M-W. Evodiamine-induced human melanoma A375–S2 cell death was mediated by PI3K/Akt/caspase and Fas-L/NF-κB signaling pathways and augmented by ubiquitin–proteasome inhibition. Toxicol Vitro. 2010;24(3):898–904.

    Article  CAS  Google Scholar 

  • Wang S, Chen M, Wang Y. Tumor suppressive activity of evodiamine in breast cancer cells via inhibition of Ras/MEK/ERK pathway and activation of PPARγ. Planta Medica. 2012;78(05):P_79.

    Article  Google Scholar 

  • Wang K-L, et al. Anti-proliferative effects of evodiamine on human breast cancer cells. PLoS One. 2013;8(6):e67297.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang S, et al. Evodiamine synergizes with doxorubicin in the treatment of chemoresistant human breast cancer without inhibiting P-glycoprotein. PLoS One. 2014;9(5):e97512.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang P, et al. Overcome cancer cell drug resistance using natural products. Evid-Based Complement Alternat Med 2015;2015.

  • Wang R, et al. Notch and Wnt/β-catenin signaling pathway play important roles in activating liver cancer stem cells. Oncotarget. 2016;7(5):5754.

    Article  PubMed  Google Scholar 

  • Wang R, et al. Evodiamine activates cellular apoptosis through suppressing PI3K/AKT and activating MAPK in glioma. Onco Targets Ther. 2018a;11:1183.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang CY, et al. Simultaneous determination of evodiamine and its four metabolites in rat plasma by LC-MS/MS and its application to a pharmacokinetic study. Biomed Chromatogr 2018b;32(7):e4219.ARTN e4219. https://doi.org/10.1002/bmc.4219.

  • Wang D, et al. Evodiamine exerts anticancer effects via induction of apoptosis and autophagy and suppresses the migration and invasion of human colon cancer cells. J Bu On:Off J Balkan Union Oncol. 2019;24(5):1824–9.

    Google Scholar 

  • Wei W-T, et al. Enhanced antitumor efficacy of gemcitabine by evodiamine on pancreatic cancer via regulating PI3K/Akt pathway. Int J Biol Sci. 2012;8(1):1.

    Article  CAS  PubMed  Google Scholar 

  • Wen B, et al. Metabolic activation of the indoloquinazoline alkaloids evodiamine and rutaecarpine by human liver microsomes: dehydrogenation and inactivation of cytochrome P450 3A4. Drug Metab Dispos. 2014;42(6):1044–54.

    Article  PubMed  Google Scholar 

  • Wen Z, et al. Evodiamine, a novel inhibitor of the Wnt pathway, inhibits the self-renewal of gastric cancer stem cells. Int J Mol Med. 2015;36(6):1657–63.

    Article  CAS  PubMed  Google Scholar 

  • Wijdeven RH, et al. Old drugs, novel ways out: Drug resistance toward cytotoxic chemotherapeutics. Drug Resist Updates. 2016;28:65–81.

    Article  Google Scholar 

  • Wu FP, et al. Profiling and identification of the metabolites of evodiamine in rats using ultra-performance liquid chromatography with linear ion trap orbitrap mass spectrometer. Trop J Pharm Res. 2016a;15(3):623–9. https://doi.org/10.4314/tjpr.v15i3.26.

    Article  CAS  Google Scholar 

  • Wu W-S, et al. Protein kinase RNA-like endoplasmic reticulum kinase-mediated Bcl-2 protein phosphorylation contributes to evodiamine-induced apoptosis of human renal cell carcinoma cells. PLoS One. 2016b;11(8):e0160484.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wu W-S, et al. Evodiamine prevents glioma growth, induces glioblastoma cell apoptosis and cell cycle arrest through JNK activation. Am J Chin Med. 2017;45(04):879–99.

    Article  PubMed  Google Scholar 

  • Xia Y-Y, et al. Simultaneous determination of evodiamine and evodine in Beagle dog plasma using liquid chromatography tandem mass spectrometry. J Asian Nat Prod Res. 2013;15(3):235–43.

    Article  CAS  PubMed  Google Scholar 

  • Xia Y, Shen S, Verma IM. NF-κB, an active player in human cancers. Cancer Immunol Res. 2014;2(9):823–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu H, et al. Preparation of evodiamine solid dispersions and its pharmacokinetics. Indian J Pharm Sci. 2011;73(3):276.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Xu S, et al. Pharmacokinetic comparisons of rutaecarpine and evodiamine after oral administration of Wu-Chu-Yu extracts with different purities to rats. J Ethnopharmacol. 2012;139(2):395–400.

    Article  CAS  PubMed  Google Scholar 

  • Yan S, et al. Difference and alteration in pharmacokinetic and metabolic characteristics of low-solubility natural medicines. Drug Metab Rev. 2018;50(2):140–60.

    Article  CAS  PubMed  Google Scholar 

  • Yang X-W, et al. Studies on the alkaloid constituents of Evodia rutaecarpa (Juss) Benth var. bodinaieri (Dode) Huang and their acute toxicity in mice. J Asian Nat Prod Res. 2006;8(8):697–703.

    Article  CAS  PubMed  Google Scholar 

  • Yang J, et al. Reactive oxygen species and nitric oxide regulate mitochondria-dependent apoptosis and autophagy in evodiamine-treated human cervix carcinoma HeLa cells. Free Radical Res. 2008a;42(5):492–504.

    Article  CAS  Google Scholar 

  • Yang J, et al. Nitric oxide activated by p38 and NF-κ B facilitates apoptosis and cell cycle arrest under oxidative stress in evodiamine-treated human melanoma A375–S2 cells. Free Radical Res. 2008b;42(1):1–11.

    Article  Google Scholar 

  • Yang ZG, Chen AQ, Liu B. Antiproliferation and apoptosis induced by evodiamine in human colorectal carcinoma cells (COLO-205). Chem Biodivers. 2009;6(6):924–33.

    Article  CAS  PubMed  Google Scholar 

  • Yang J, et al. Evodiamine inhibits STAT3 signaling by inducing phosphatase shatterproof 1 in hepatocellular carcinoma cells. Cancer Lett. 2013;328(2):243–51.

    Article  CAS  PubMed  Google Scholar 

  • Yang K, et al. The evolving roles of canonical WNT signaling in stem cells and tumorigenesis: implications in targeted cancer therapies. 2016a;96(2):116-136

  • Yang K, et al. The evolving roles of canonical WNT signaling in stem cells and tumorigenesis: implications in targeted cancer therapies. Lab Invest. 2016b;96(2):116–36.

    Article  CAS  PubMed  Google Scholar 

  • Yang F, et al. Anti-tumor effect of evodiamine by inducing Akt-mediated apoptosis in hepatocellular carcinoma. Biochem Biophys Res Commun. 2017a;485(1):54–61.

    Article  CAS  PubMed  Google Scholar 

  • Yang W, et al. Evaluation of the cardiotoxicity of evodiamine in vitro and in vivo. Molecules. 2017b;22(6):943.

    Article  PubMed  PubMed Central  Google Scholar 

  • Yang X, et al. Head and neck cancers promote an inflammatory transcriptome through coactivation of classic and alternative NF-κB pathways. Cancer Immunol Res. 2019;7(11):1760–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang S, et al. Evodiamine exerts anticancer effects against 143B and MG63 cells through the Wnt/β-catenin signaling pathway. Cancer Manag Res. 2020a;12:2875.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang X, et al. Evodiamine suppresses Notch3 signaling in lung tumorigenesis via direct binding to γ-secretases. Phytomedicine. 2020b;68:153176.

    Article  CAS  PubMed  Google Scholar 

  • Yu H, et al. Pharmacological actions of multi-target-directed evodiamine. Molecules. 2013;18(2):1826–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yuan X, et al. Notch signaling: an emerging therapeutic target for cancer treatment. Cancer Lett. 2015;369(1):20–7.

    Article  CAS  PubMed  Google Scholar 

  • Yuan R, et al. Natural products to prevent drug resistance in cancer chemotherapy: a review. Ann N Y Acad Sci. 2017a;1401(1):19–27.

    Article  PubMed  Google Scholar 

  • Yuan X-L, et al. Cytological assessments and transcriptome profiling demonstrate that evodiamine inhibits growth and induces apoptosis in a renal carcinoma cell line. Sci Rep. 2017b;7(1):1–10.

    Article  Google Scholar 

  • Yuan Y, et al. Evodiamine inhibits apoptosis of human osteosarcoma MG-63 cells by blocking wnt/β-catenin signaling. J Int Oncol. 2017c;44(2):86.

    Google Scholar 

  • Yue G, et al. Synergistic anticancer effects of polyphyllin I and evodiamine on freshly-removed human gastric tumors. PLoS One. 2013;8(6):e65164.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, et al. Intracellular regulation of evodiamine-induced A375–S2 cell death. Biol Pharm Bull. 2003;26(11):1543–7.

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, et al. Evodiamine induces tumor cell death through different pathways: apoptosis and necrosis. Acta Pharmacol Sin. 2004;25(1):83.

    PubMed  Google Scholar 

  • Zhang C, et al. Evodiamine induces caspase-dependent apoptosis and S phase arrest in human colon lovo cells. Anticancer Drugs. 2010;21(8):766–76.

    Article  CAS  PubMed  Google Scholar 

  • Zhang T, et al. Evodiamine induces apoptosis and enhances TRAIL-induced apoptosis in human bladder cancer cells through mTOR/S6K1-mediated downregulation of Mcl-1. Int J Mol Sci. 2014;15(2):3154–71.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang J, Tian X-J, Xing J. Signal transduction pathways of EMT induced by TGF-β, SHH, and WNT and their crosstalks. J Clin Med. 2016a;5(4):41.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang X, et al. A preliminary study of pharmacokinetics of evodiamine hydroxypropyl-β-cyclodextrin inclusion complex. J South Med Univ. 2016b;36(4):548–51.

    CAS  Google Scholar 

  • Zhang YT, et al. Effect of evodiamine on CYP enzymes in rats by a cocktail method. Pharmacology. 2016c;97(5–6):218–23. https://doi.org/10.1159/000443178.

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Zhang Q, Chen H. BCL9 promotes epithelial mesenchymal transition and invasion in cisplatin resistant NSCLC cells via β-catenin pathway. Life Sci. 2018a;208:284–94.

    Article  CAS  PubMed  Google Scholar 

  • Zhang Z, et al. Characterization of the in vitro metabolic profile of evodiamine in human liver microsomes and hepatocytes by UHPLC-Q exactive mass spectrometer. Front Pharmacol. 2018b;9:130. https://doi.org/10.3389/fphar.2018.00130.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao L-C, et al. Evodiamine induces apoptosis and inhibits migration of HCT-116 human colorectal cancer cells. Int J Mol Sci. 2015;16(11):27411–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao L, et al. Modulatory effect of evodiamine on JAK2/STAT3 signal pathway in HCT-116 cells. Chin Pharm Bull 2015;(10):1394–1397, 1398.

  • Zhao S, et al. Evodiamine inhibits proliferation and promotes apoptosis of hepatocellular carcinoma cells via the Hippo-yes-associated protein signaling pathway. Life Sci. 2020;251:117424.

    Article  CAS  PubMed  Google Scholar 

  • Zheng Y, et al. Evodiamine induces apoptosis in pancreatic carcinoma PANC-1 cells via NF-κB inhibition. ||| Bangladesh J Pharmacol. 2013;8(1):8–14.

    Google Scholar 

  • Zhong Z-F, et al. Anti-proliferative activity and cell cycle arrest induced by evodiamine on paclitaxel-sensitive and-resistant human ovarian cancer cells. Sci Rep. 2015;5:16415.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou Y, Hu J. Evodiamine induces apoptosis, G2/M cell cycle arrest, and inhibition of cell migration and invasion in human osteosarcoma cells via Raf/MEK/ERK signalling pathway. Med Sci Monit: Int Med J Exp Clin Res. 2018;24:5874.

    Article  CAS  Google Scholar 

  • Zhou P, et al. Evodiamine inhibits migration and invasion by Sirt1-mediated post-translational modulations in colorectal cancer. Anticancer Drugs. 2019;30(6):611.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu B, et al. Induction of phosphatase shatterproof 2 by evodiamine suppresses the proliferation and invasion of human cholangiocarcinoma. Int J Biochem Cell Biol. 2019a;108:98–110.

    Article  CAS  PubMed  Google Scholar 

  • Zhu H, et al. Growth inhibitor of human hepatic carcinoma HepG2 cells by evodiamine is associated with downregulation of PRAME. Naunyn Schmiedebergs Arch Pharmacol. 2019b;392(12):1551–60.

    Article  CAS  PubMed  Google Scholar 

  • Zou Y, et al. Apoptosis of human non-small-cell lung cancer A549 cells triggered by evodiamine through MTDH-dependent signaling pathway. Tumor Biology. 2015;36(7):5187–93.

    Article  CAS  PubMed  Google Scholar 

  • Zou L, et al. Preparation, characterization, and anticancer efficacy of evodiamine-loaded PLGA nanoparticles. Drug Delivery. 2016;23(3):898–906.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the National Institute of Technology Rourkela, Odisha, India, for providing laboratory and other facilities to carry out this work.

Funding

Department of Science and Technology, Science and Engineering Research Board (DST, SERB), New Delhi, India (Grant Number: ECR/2016/000792) and Ministry of human resource and development (MHRD), New Delhi, and Department of Science and Technology, Odisha, India (Grant No-1201).

Author information

Authors and Affiliations

  1. Cancer Drug Resistance Laboratory, Department of Life Science, National Institute of Technology Rourkela, Odisha-769008, Rourkela, India

    Munmun Panda, Surya Kant Tripathi & Bijesh K. Biswal

  2. Department of Biology, Science Faculty, Selcuk University, Konya, Turkey

    Gokhan Zengin

Authors
  1. Munmun Panda
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Surya Kant Tripathi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gokhan Zengin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bijesh K. Biswal
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The first draft of the manuscript was prepared by MP. The bioavailability and pharmacokinetics section and Fig. 1 of this manuscript were written and drawn by SKT, and GZ edited the manuscript. BKB guided and edited the manuscript. Lastly, all authors approved the final version of the manuscript.

Corresponding author

Correspondence to Bijesh K. Biswal.

Ethics declarations

Ethics approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

All the authors agreed to publish this manuscript.

Competing interests

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Panda, M., Tripathi, S.K., Zengin, G. et al. Evodiamine as an anticancer agent: a comprehensive review on its therapeutic application, pharmacokinetic, toxicity, and metabolism in various cancers. Cell Biol Toxicol 39, 1–31 (2023). https://doi.org/10.1007/s10565-022-09772-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10565-022-09772-8

Keywords

Search

Navigation