Abstract
Notoginsenoside R7 was isolated from Panax notoginseng, a plant used commonly in traditional Chinese medicine. We investigated the anti-cancer effects of R7 in HeLa cells in vitro and in vivo, and explored the underlying mechanisms of action. R7 dose-dependently inhibited HeLa cell proliferation and induced apoptosis in vitro, In silico docking-based screening assays showed that R7 can directly bind Akt. Pretreatment with the Akt inhibitor LY294002 synergistically enhanced the R7 anti-proliferation and anti-apoptosis effects in HeLa cells, confirming that R7 acts through the PI3K/Akt pathway. Consistent with the in vitro findings, R7 exerted anti-tumor effects in a mouse xenograft model by targeting PI3K (PTEN) and Akt, activating the pro-apoptotic Bcl-2 family and, subsequently, caspase family members. R7 treatment activated PTEN and downregulated mTOR phosphorylation without affecting mTOR expression, though regulatory-associated protein of mTOR (raptor) expression declined. Our study suggests that R7 is a promising chemotherapeutic agent for the treatment of cervical cancer and other PI3K/PTEN/Akt/mTOR signaling-associated tumors.
Highlights
Due to their therapeutic efficacies and minimal adverse effects, biologically active natural compounds are gaining popularity as potential first-line treatments [1, 2]
Our study suggests that R7 is a promising chemotherapeutic agent for the treatment of cervical cancer and other PI3K/PTEN/Akt/mTOR signaling-associated tumors
The present study found that the P. notoginseng compound, R7, inhibited HeLa cell proliferation and induced apoptosis in a dose-dependent manner
Summary
Due to their therapeutic efficacies and minimal adverse effects, biologically active natural compounds are gaining popularity as potential first-line treatments [1, 2]. Notoginsenoside R7 (R7, Panaxadiol-3-O-β-Dglucopyranoside) is a triterpenoid saponin isolated from the dried root and rhizome of Panax notoginseng (Burk.) F.H.Chen, which is found mainly in south western China. The anti-tumor activities of triterpenoid saponins suggest that ginsenosides Rg3, Rg5, and Rh2 could induce www.impactjournals.com/oncotarget cancer cell apoptosis and inhibit invasion, metastasis, and cell cycle progression [7,8,9,10]. Mechanistic studies suggest that notoginsenosides downregulate vascular endothelial growth factor (VEGF) expression, inhibit NF-κB activity, and promote autophagy [11]. No pharmacological bioactivity has far been reported for R7, and the underlying mechanisms of its anti-cancer effects remain unclear
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