title: Triptolide inhibits tumor growth by induction of cellular senescence.
abstract: Cellular senescence, an irreversible growth arrest of cells, is involved in protection against cancer. Triptolide (TPL) plays an important role in immunosuppressive, anti-fertility, anti-cystogenesis and anticancer activities. However, effect and mechanism of TPL on cellular senescence-associated antitumor is rarely reported. Herein HepG2 cells were used to explore the effect of TPL on tumor growth and cellular senescence. We showed that TPL inhibited tumor cell proliferation and growth in vitro and in vivo, accelerated cellular senescence and arrested cells at G0/G1 phase. We further demonstrated that TPL accelerated HepG2 cell senescence by regulating the AKT pathway. In addition, TPL could also enhance cellular senescence and inhibit tumor growth by negatively regulating human telomerase reverse transcriptase (hTERT) signaling pathway. These findings reveal a regulatory mechanism of TPL on cellular senescence, indicating that TPL promotes HepG2 cell senescence through AKT pathway and hTERT pathway simultaneously. Altogether, TPL-induced senescence can be regarded as a promising strategy for anticancer therapy and drug development.
authors.affiliation: Department of General Surgery and Liver Transplant Center, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors.forename: Ruidong
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of General Surgery and Liver Transplant Center, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Bioscience Research Center, Shanghai 200120, P.R. China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of General Surgery and Liver Transplant Center, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors.forename: Conghuan
authors.initials: C
authors.lastname: Shen
authors.affiliation: Department of General Surgery and Liver Transplant Center, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors.forename: Quanbao
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Bioscience Research Center, Shanghai 200120, P.R. China.
authors.forename: Yihong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of General Surgery and Liver Transplant Center, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors.forename: Zhengxin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Bioscience Research Center, Shanghai 200120, P.R. China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of General Surgery and Liver Transplant Center, Huashan Hospital, Fudan University, Shanghai 200040, P.R. China.
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Tao
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D016922:Cellular Senescence / Q000187:drug effects*; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009369:Neoplasms / Q000473:pathology*; D010616:Phenanthrenes / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D004224:Diterpenes; D004852:Epoxy Compounds; D010616:Phenanthrenes; C001899:triptolide