Ginsenoside PPD's Antitumor Effect via Down-Regulation of mTOR Revealed by Super-Resolution Imaging.
Derived fromPanax 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.
Department of Otolaryngology Head and Neck Surgery, The Second Hospital, Jilin University, Changchun 13041, Jilin, China. tengbo1975@163.com.
Bo
B
Teng
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 13021, Jilin, China. jiangjg@ciac.ac.cn.
Junguang
J
Jiang
School of Nursing, Jilin University, Changchun 13021, Jilin, China. zhao_lj@jlu.edu.cn.
Lijing
L
Zhao
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 13021, Jilin, China. gaojing@ciac.ac.cn.
Jing
J
Gao
Department of Otolaryngology Head and Neck Surgery, The Second Hospital, Jilin University, Changchun 13041, Jilin, China. Jack.c.j.y@163.com.
Junyu
J
Chen
Department of Otolaryngology Head and Neck Surgery, The Second Hospital, Jilin University, Changchun 13041, Jilin, China. keke_liu@foxmail.com.
Zhe
Z
Liu
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 13021, Jilin, China. hdwang@ciac.ac.cn.
Hongda
H
Wang
Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA. binfeng@pitt.edu.
Binfeng
B
Lu
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D004354:Drug Screening Assays, Antitumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D008853:Microscopy; D012502:Sapogenins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D013269:Stochastic Processes; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; D012502:Sapogenins; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; C062916:protopanaxadiol
PPD; antitumor; dSTORM; laryngeal cancer; mTOR