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Gypenosides, the cancer buster from Gynostemma pentaphyllum (Thunb.) Makino and the apoptotic pathways: a review

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Abstract

Gynostemma pentaphyllum is consumed as herbal tea by the Chinese. It has been extensively studied in the past 20 years and the major secondary metabolites, gypenosides (Gyp) are known to exhibit many medicinal properties such as anti-cancers, anti-inflammatory, antipyretic, anti-hyperlipidemic, and anti-diabetic. This review summarizes the effect of Gyp towards various cancer cells, and reports the five apoptotic pathways taken by Gyp in inhibiting the cancer cell growth and development, namely (1) blocking of cancer cell initiation, (2) apoptosis via Ca2+ overload, (3) causing mitochondrial membrane depolarization via caspase dependent and independent pathways, (4) inhibition of DNA repair genes by downregulation and (5) anti-metastatic effect by downregulating the synthesis of numerous tumor-associated metastatic-related proteins. Both in vitro and in vivo studies of Gyp showed that it could inhibit cancer cell growth and development. These results showed that Gyp has a great potential to be used as herbal remedy and an alternative treatment for cancer.

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Abbreviations

AIF:

Apoptosis inducing factor

Akt:

Alpha serine/threonine-protein kinase

ATM:

Ataxia telangiectasia mutated

ATR:

Ataxia-telangiectasia and Rad3-related

BRCA1:

Breast cancer gene

COX-2:

Cyclooxygenase-2

DNAPK:

DNA-dependent serine/threonine protein kinase

ECM:

Extracellular matrix

Endo G:

Endonuclease G

ER:

Endoplasmic reticulum

ERK1/2:

Extracellular signal-regulated kinase 1/2

FAK:

Focal adhesion kinase

Gyp:

Gypenosides

H2O2 :

Hydrogen peroxide

IP3R:

Inositol 1,4,5-triphosphate receptors

IR:

Ionizing

MANA:

Methyl-n-amyl nitrosamine

MMP-2:

Matrix metalloproteinase-2

MMP-9:

Matrix metalloproteinase-9

NF-κB:

Nuclear factor-kappa B

ROS:

Reactive oxygen species

SERCA:

Sarco/ER-Ca2+-ATPase

SOS:

Sevenless homolog

uPA:

Urokinase-type plasminogen activator

UV:

Ultraviolet

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Acknowledgments

The authors would like to thank Prof Basil for the permission to reuse the table, Elsevier and John and Wiley and Sons for the license for the figures. The authors would like to thank UCSI University for scientific databases access for the literatures used in the review paper.

Authors’ contributions

YLC wrote the manuscript; HCW critically revised the manuscript. Both authors have read and approved the final manuscript.

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Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, UCSI University, No.1, Jalan Menara Gading, UCSI Heights, 56000 Cheras, Kuala Lumpur, Malaysia

    Yik-Ling Chew

  2. Klinik für Hämatologie, Universitäts Spital Zürich, Schmelzbergstrasse 12, 8091, Zürich, Switzerland

    Hui-Chyn Wong

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  1. Yik-Ling Chew
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Correspondence to Yik-Ling Chew.

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Chew, YL., Wong, HC. Gypenosides, the cancer buster from Gynostemma pentaphyllum (Thunb.) Makino and the apoptotic pathways: a review. Orient Pharm Exp Med 16, 153–164 (2016). https://doi.org/10.1007/s13596-016-0231-0

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