Ginsenoside PPD's Antitumor Effect via Down-Regulation of mTOR Revealed by Super-Resolution Imaging.
Derived from Panax ginseng, the natural product 20(S)-Protopanaxadiol (PPD) has been reported for its cytotoxicity against several cancer cell lines. The molecular mechanism is, however, not well understood. Here we show that PPD significantly inhibits proliferation, induces apoptosis and causes G2/M cell cycle arrest in human laryngeal carcinoma cells (Hep-2 cells). PPD also decreases the levels of proteins related to cell proliferation. Moreover, PPD-induced apoptosis is characterized by a dose-dependent down-regulation of Bcl-2 expression and up-regulation of Bax, and is accompanied by the activation of Caspase-3 as well. Further molecular mechanism is revealed by direct stochastic optical reconstruction microscopy (dSTORM)-a novel high-precision localization microscopy which enables effective resolution down to the order of 10 nm. It shows the expression and spatial arrangement of mTOR and its downstream effectors, demonstrating that this ginsenoside exerts its excellent anticancer effects via down-regulation of mTOR signaling pathway in Hep-2 cells. Taken together, our findings elucidate that the antitumor effect of PPD is associated with its regulation of mTOR expression and distribution, which encourages further studies of PPD as a promising therapeutic agent against laryngeal carcinoma.
['Teng|Bo|B|', 'Jiang|Junguang|J|', 'Zhao|Lijing|L|', 'Gao|Jing|J|', 'Chen|Junyu|J|', 'Liu|Zhe|Z|', 'Wang|Hongda|H|', 'Lu|Binfeng|B|']
D000972:Antineoplastic Agents, Phytogenic D002453:Cell Cycle D049109:Cell Proliferation D002470:Cell Survival D015536:Down-Regulation D004354:Drug Screening Assays, Antitumor D015972:Gene Expression Regulation, Neoplastic D056945:Hep G2 Cells D006801:Humans D008853:Microscopy D012502:Sapogenins D015398:Signal Transduction D013269:Stochastic Processes D058570:TOR Serine-Threonine Kinases
PPD antitumor mTOR dSTORM laryngeal cancer