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Plant Flavone Apigenin: an Emerging Anticancer Agent

  • Cancer Chemoprevention (R Agarwal, Section Editor)
  • Published:
Current Pharmacology Reports Aims and scope Submit manuscript

Abstract

Research in cancer chemoprevention provides convincing evidence that increased intake of vegetables and fruits may reduce the risk of several human malignancies. Phytochemicals present therein provide beneficial anti-inflammatory and antioxidant properties that serve to improve the cellular microenvironment. Compounds known as flavonoids categorized anthocyanidins, flavonols, flavanones, flavonols, flavones, and isoflavones have shown considerable promise as chemopreventive agents. Apigenin (4′,5,7-trihydroxyflavone), a major plant flavone, possessing antioxidant, anti-inflammatory, and anticancer properties affecting several molecular and cellular targets used to treat various human diseases. Epidemiologic and case-control studies have suggested apigenin reduces the risk of certain cancers. Studies demonstrate that apigenin retains potent therapeutic properties alone and/or increases the efficacy of several chemotherapeutic drugs in combination on a variety of human cancers. Apigenin’s anticancer effects could also be due to its differential effects in causing minimal toxicity to normal cells with delayed plasma clearance and slow decomposition in the liver increasing the systemic bioavailability in pharmacokinetic studies. Here we discuss the anticancer role of apigenin highlighting its potential activity as a chemopreventive and therapeutic agent. We also highlight the current caveats that preclude apigenin for its use in the human trials.

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Abbreviations

4-HPR:

N-(4-Hydroxyphenyl) retinamide

5-FU:

Fluorouracil

ACF:

Aberrant crypt foci

ADM:

Doxorubicin

ADP:

Adenosine di-phosphate

AICR:

American Institute for Cancer Research

AOM:

Azoxymethane

APC:

Adenomatous polyposis coli

ATF3:

Activating transcription factor 3

BCRP:

Breast cancer resistance protein

CK2:

Casein kinase 2

COX-2:

Cyclooxygenase-2

DISC:

Death-inducing signaling complex

DOX:

Doxorubicin

DR4:

Death receptor 4

EGFR:

Epidermal growth factor receptor

ERK:

Extracellular regulated kinase

FAK:

Focal adhesion kinase

GADD45:

DNA fragmentation factor-45

Gli1:

Glioma-associated oncogene 1

GLUT1:

Glucose transporter 1

GSTA1:

Glutathione S-transferase A1

HDAC:

Histone deacetylase

HIF-1α:

Hypoxia-inducible factor 1-alpha

hTERT:

Telomerase reverse transcriptase

ICAM-1:

Intercellular adhesion molecule-1

IFNAR1:

Type I interferon receptor 1

IFN-γ:

Interferon gamma

IGF:

Insulin-like growth factor

IL6:

Interleukin-6

JAK:

Janus kinase

JNK:

c-Jun amino-terminal kinase

KLF4:

Krüpple-like factor 4

MAPK:

Mitogen-activated protein kinases

MMP:

Matrix metalloproteinases

NADPH:

Nicotinamide adenine dinucleotide phosphate

NF-ĸB:

Nuclear factor-kappaB

NIS:

Na+/I− symporter

NSCLC:

Non-small cell lung cancer

ODC:

Ornithine decarboxylase

PARP:

Poly (ADP-ribose) polymerase

PD-L1:

Programmed death-ligand 1

PDPK FA:

Proline-directed protein kinase FA

PI3K:

Phosphatidylinositol-4,5-bisphosphate 3-kinase

PKC:

Protein kinase C

PLGA:

Poly-lactic-co-glycolide

PMA:

Protein kinase C-activating phorbol ester

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

Stat:

Signal transducer and activator of transcription

TGF-β:

Transforming growth factor-beta

TRAIL:

Tumor necrosis factor-related apoptosis-inducing ligands

TRAMP:

Transgenic adenocarcinoma of the mouse prostate

UGT1A1:

UDP-glucuronosyltransferase 1–1

VEGF:

Vascular endothelial growth factor

WCRF:

World Cancer Research Fund

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Acknowledgements

We sincerely apologize to those investigators whose work could not be cited due to space constraints.

Funding

The original work from author’s laboratory outlined in this review was supported by VA Merit Review 1I01BX002494; United States Public Health Service Grants RO1CA108512, R21CA193080, and R03CA186179 and Department of Defense grant W81XWH-15-1-0558 to SG.

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Authors and Affiliations

  1. Department of Urology, The James and Eilleen Dicke Laboratory, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH, 44106, USA

    Eswar Shankar, Karishma Gupta & Sanjay Gupta

  2. Department of Urology, The Urology Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, 44106, USA

    Eswar Shankar, Karishma Gupta & Sanjay Gupta

  3. Department of Biology, School of Undergraduate Studies, Case Western Reserve University, Cleveland, OH, 44106, USA

    Aditi Goel

  4. Department of Nutrition, Case Western Reserve University, Cleveland, OH, 44106, USA

    Sanjay Gupta

  5. Division of General Medical Sciences, Case Comprehensive Cancer Center, Cleveland, OH, 44106, USA

    Sanjay Gupta

  6. Department of Urology, Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, OH, 44106, USA

    Sanjay Gupta

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  1. Eswar Shankar
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  2. Aditi Goel
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Correspondence to Sanjay Gupta.

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This article is part of the Topical Collection on Cancer Chemoprevention

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Shankar, E., Goel, A., Gupta, K. et al. Plant Flavone Apigenin: an Emerging Anticancer Agent. Curr Pharmacol Rep 3, 423–446 (2017). https://doi.org/10.1007/s40495-017-0113-2

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