Ginseng saponin metabolite 20(S)-protopanaxadiol inhibits tumor growth by targeting multiple cancer signaling pathways
Language: 
English
Abstract: 

Plant-derived active constituents and their semi-synthetic or synthetic analogs have served as major sources of anticancer drugs. 20(S)-protopanaxadiol (PPD) is a metabolite of ginseng saponin of both American ginseng (Panax quinquefolius L.) and Asian ginseng (Panax ginseng C.A. Meyer). We previously demonstrated that ginsenoside Rg3, a glucoside precursor of PPD, exhibits anti-proliferative effects on HCT116 cells and reduces tumor size in a xenograft model. Our subsequent study indicated that PPD has more potent antitumor activity than that of Rg3 in vitro although the mechanism underlying the anticancer activity of PPD remains to be defined. Here, we investigated the mechanism underlying the anticancer activity of PPD in human cancer cells in vitro and in vivo. PPD was shown to inhibit growth and induce cell cycle arrest in HCT116 cells. The in vivo studies indicate that PPD inhibits xenograft tumor growth in athymic nude mice bearing HCT116 cells. The xenograft tumor size was significantly reduced when the animals were treated with PPD (30 mg/kg body weight) for 3 weeks. When the expression of previously identified Rg3 targets, A kinase (PRKA) anchor protein 8 (AKAP8L) and phosphatidylinositol transfer protein α (PITPNA), was analyzed, PPD was shown to inhibit the expression of PITPNA while upregulating AKAP8L expression in HCT116 cells. Pathway-specific reporter assays indicated that PPD effectively suppressed the NF-κB, JNK and MAPK/ERK signaling pathways. Taken together, our results suggest that the anticancer activity of PPD in colon cancer cells may be mediated through targeting NF-κB, JNK and MAPK/ERK signaling pathways, although the detailed mechanisms underlying the anticancer mode of PPD action need to be fully elucidated.

Author(s): 
Gao, Jian-Li
Lv, Gui-Yuan
He, Bai-Cheng
Zhang, Bing-Qiang
Zhang, Hongyu
Wang, Ning
Wang, Chong-Zhi
Du, Wei
Yuan, Chun-Su
He, Tong-Chuan
Item Type: 
Journal Article
Publication Title: 
Oncology Reports
Journal Abbreviation: 
Oncol. Rep.
Publication Date: 
Jul 2013
Publication Year: 
2013
Pages: 
292-298
Volume: 
30
Issue: 
1
ISSN: 
1791-2431
DOI: 
10.3892/or.2013.2438
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 23633038 PMCID: PMC3729206

Turabian/Chicago Citation

Jian-Li Gao, Gui-Yuan Lv, Bai-Cheng He, Bing-Qiang Zhang, Hongyu Zhang, Ning Wang, Chong-Zhi Wang, Wei Du, Chun-Su Yuan and Tong-Chuan He. Jul 2013. "Ginseng saponin metabolite 20(S)-protopanaxadiol inhibits tumor growth by targeting multiple cancer signaling pathways." Oncology Reports 30: 1: 292-298. 10.3892/or.2013.2438.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.3892/or.2013.2438 | issn = 1791-2431 | volume = 30 | pages = 292-298 | last = Gao | first = Jian-Li | coauthors = Lv, Gui-Yuan, He, Bai-Cheng, Zhang, Bing-Qiang, Zhang, Hongyu, Wang, Ning, Wang, Chong-Zhi, Du, Wei, Yuan, Chun-Su, He, Tong-Chuan | title = Ginseng saponin metabolite 20(S)-protopanaxadiol inhibits tumor growth by targeting multiple cancer signaling pathways | journal = Oncology Reports | date = Jul 2013 | pmid = | pmc = }} </ref>