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Tanshinone IIA targeting cell signaling pathways: a plausible paradigm for cancer therapy

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Abstract

Natural compounds originating from plants offer a wide range of pharmacological potential and have traditionally been used to treat a wide range of diseases including cancer. Tanshinone IIA (Tan IIA), a bioactive molecule found in the roots of the Traditional Chinese Medicine (TCM) herb Salvia miltiorrhiza, has been shown to have remarkable anticancer properties through several mechanisms, such as inhibition of tumor cell growth and proliferation, metastasis, invasion, and angiogenesis, as well as induction of apoptosis and autophagy. It has demonstrated excellent anticancer efficacy against cell lines from breast, cervical, colorectal, gastric, lung, and prostate cancer by modulating multiple signaling pathways including PI3K/Akt, JAK/STAT, IGF-1R, and Bcl-2–Caspase pathways. This review focuses on the role of Tan IIA in the treatment of various cancers, as well as the underlying molecular mechanisms.

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Data sharing does not apply to this article as no datasets were generated or analyzed during the current study.

Abbreviations

AACT:

Acetyl-CoA C-acetyltransferase

Akt:

Protein kinase B

AML:

Acute myeloid leukemia

AMPK:

AMP-activated protein kinase

AP-1:

Activator protein 1

ATF6:

Activating transcription factor 6

AURKA:

Aurora kinase A

BAX:

Bcl-2-associated X protein

Bcl-XL:

B-cell lymphoma-extra large

bFGF:

Basic fibroblast growth factor

BIP:

Binding immunoglobulin protein

CD80:

Cluster of differentiation 80

Cdc25A:

Cell division cycle 25 A

CDK:

Cyclin-dependent kinases

CHOP:

C/EBP homologous protein

CML:

Chronic myeloid leukemia

CPP:

Copalyl diphosphate

CRC:

Colorectal cancer cells

CTLA-4:

Cytotoxic T-lymphocyte associated antigen-4

DMAPP:

Dimethylallyl pyrophosphate

DXS:

1-Deoxy-D-xylulose-5-phosphate synthase

EGFR:

Epithelial growth factor receptor

eIF2α:

Eukaryotic translation initiation factor 2α

ERK:

Extracellular signal-related kinase

FLIPs:

FLICE inhibitory protein

FOXM1:

Forkhead box protein M1

FPP:

Farnesyl diphosphate

FPPS:

FPP synthase

G3P:

Glyceraldehyde-3-phosphate

GADD153:

α Growth arrest and DNA damage-inducible gene 153

GFAP:

Glial fibrillary acidic protein

GGPP:

Geranylgeranyl diphosphate

GGPPS:

GGPP synthase

GPP:

Geranyl diphosphate

GPPS:

GPP synthase

HER2:

Receptor tyrosine-protein kinase erbB-2

HIF-1 α:

Hypoxia-inducible factor 1 α

HMGR:

3-Hydroxy-3-methylglutaryl-CoA reductase

HPV:

Human papillomavirus

IGF-1:

Insulin-like growth factor- 1

IL-6:

Interleukin 6

IL-8:

Pro-inflammatory cytokine interleukin-8

IPI:

IPP isomerase

IPP:

Isopentenyl pyrophosphate

IRE1:

Inositol-requiring gene 1

JAK:

Janus-activated kinase

JNK:

C-jun N-terminal kinase

KEGG:

KEGG: Kyoto Encyclopedia of Genes and Genomes

Ki-67:

Antigen KI-67

MAPK:

Mitogen-activated protein kinase

MEP:

Methylerythritol phosphate

MFF:

Mitochondrial fission factor

MMP-2:

Matrix metalloproteinase 2

mTOR:

Mammalian target of rapamycin

MVA:

Mevalonate

NF-κB:

Nuclear factor kappa B

Notch-1:

Notch homolog 1

NSCLC:

Non‐small cell lung cancer

PARP:

Poly(ADP ribose) polymerase

PC12:

Pheochromocytoma cells

PCNA:

Proliferating cell nuclear antigen

PD-1:

Programmed cell death-1 receptor

PD-L1:

Programmed cell death-ligand 1

PERK:

Protein kinase RNA-like endoplasmic reticulum kinase

PI3K:

Phosphatidylinositol-3-kinase

PKC:

Protein kinase C

PLC:

Phospholipase C

RAS:

Rat sarcoma virus

Rb:

Retinoblastoma

Skp2:

S-phase kinase-associated protein 2

SmCPS:

CPP synthase

SmKSL:

Kaurene synthase-like cyclase

STAT3:

Signal transducer and activator of transcription 3

Tan IIA:

Tanshinone IIA

TCM:

Traditional Chinese Medicine

TIMP:

Tissue inhibitor of matrix metalloproteinase protein

uPA:

Urokinase plasminogen activator

VEGF/VEGFR2:

Vascular endothelial growth factor/VEGF receptor 2

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Acknowledgements

The authors gratefully acknowledge the Department of Biological Sciences at Aliah University in Kolkata, India, for providing essential research facilities. SSMA sincerely acknowledges the Council of Scientific and Industrial Research (CSIR), Government of India for financial help in the form of a Junior Research Fellowship (JRF).

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Authors and Affiliations

  1. Applied Biochemistry Laboratory, Department of Biological Sciences, Aliah University, Kolkata, 700160, India

    Syed Sahajada Mahafujul Alam, Arijit Samanta & Mehboob Hoque

  2. National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, 560065, India

    Faizan Uddin

  3. Clinical and Applied Genomics (CAG) Laboratory, Department of Biological Sciences, Aliah University, Kolkata, 700160, India

    Safdar Ali

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SSMA, AS, and FU wrote portions of the initial draft of the paper and modified the draft. SSMA, AS, and MH contributed to the figures. SA and MH edited the draft of the paper and made final changes to the final version before submission. All authors have read and agreed to the published version of the manuscript.

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Alam, S.S.M., Samanta, A., Uddin, F. et al. Tanshinone IIA targeting cell signaling pathways: a plausible paradigm for cancer therapy. Pharmacol. Rep 75, 907–922 (2023). https://doi.org/10.1007/s43440-023-00507-y

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