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. 2012 Feb 28:3:25.
doi: 10.3389/fphar.2012.00025. eCollection 2012.

Ginsenosides as Anticancer Agents: In vitro and in vivo Activities, Structure-Activity Relationships, and Molecular Mechanisms of Action

Subhasree Ashok Nag  1 , Jiang-Jiang Qin, Wei Wang, Ming-Hai Wang, Hui Wang, Ruiwen Zhang
Affiliations

Ginsenosides as Anticancer Agents: In vitro and in vivo Activities, Structure-Activity Relationships, and Molecular Mechanisms of Action

Subhasree Ashok Nag et al. Front Pharmacol. .

Abstract

Conventional chemotherapeutic agents are often toxic not only to tumor cells but also to normal cells, limiting their therapeutic use in the clinic. Novel natural product anticancer compounds present an attractive alternative to synthetic compounds, based on their favorable safety and efficacy profiles. Several pre-clinical and clinical studies have demonstrated the anticancer potential of Panax ginseng, a widely used traditional Chinese medicine. The anti-tumor efficacy of ginseng is attributed mainly to the presence of saponins, known as ginsenosides. In this review, we focus on how ginsenosides exert their anticancer effects by modulation of diverse signaling pathways, including regulation of cell proliferation mediators (CDKs and cyclins), growth factors (c-myc, EGFR, and vascular endothelial growth factor), tumor suppressors (p53 and p21), oncogenes (MDM2), cell death mediators (Bcl-2, Bcl-xL, XIAP, caspases, and death receptors), inflammatory response molecules (NF-κB and COX-2), and protein kinases (JNK, Akt, and AMP-activated protein kinase). We also discuss the structure-activity relationship of various ginsenosides and their potentials in the treatment of various human cancers. In summary, recent advances in the discovery and evaluation of ginsenosides as cancer therapeutic agents support further pre-clinical and clinical development of these agents for the treatment of primary and metastatic tumors.

Keywords: Panax genus; Panax ginseng; anticancer activities; clinical trials; ginsenosides; molecular mechanism; pre-clinical pharmacology; structure–activity relationship.

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Figures

Figure 1
Figure 1
Chemical structures of protopanaxadiol-type ginsenosides.
Figure 2
Figure 2
Chemical structures of protopanaxatriol-type, ocotillol-type and oleanic acid-type ginsenosides.
Figure 3
Figure 3
Possible cellular and molecular mechanisms of ginsenosides aginst cancer. CDKs, cyclin-dependent kinases; MDM2, murine double minute-2; VEGF, vascular endothelial growth factor; bFGF, basic fibroblast growth factor; PDGF, platelet derived growth factor, MMP, matrix metalloproteinase; IAP, inhibitory apoptotic protein; TNF, tumor necrosis factor; NF-κB, nuclear factor κB; PI3K, Phosphatidylinositol 3-kinase; HIF-1, hypoxia-inducible factor-1; ERK, extracellular signal-regulated kinase; NRF2, nuclear factor (erythroid-derived 2)-like; AMPK, 5′ AMP-activated protein kinase; EGF, epithelial growth factor; ↑, upregulation; ↓, downregulation.
Figure 4
Figure 4
Cell signaling pathways involved in cell cycle arrest targeted by selected ginsenosides. Rb, retinoblastoma protein.
Figure 5
Figure 5
Cell signaling pathways involved in apoptotic response targeted by selected ginsenosides. KRG, Korean red ginseng; AG: American ginseng.
Figure 6
Figure 6
Signal Transduction pathways targeted by selected ginsenosides.
See this image and copyright information in PMC

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