title: Teroxirone inhibited growth of human non-small cell lung cancer cells by activating p53.
abstract: In this work, we demonstrated that the growth of human non-small-cell-lung-cancer cells H460 and A549 cells can be inhibited by low concentrations of an epoxide derivative, teroxirone, in both in vitro and in vivo models. The cytotoxicity was mediated by apoptotic cell death through DNA damage. The onset of ultimate apoptosis is dependent on the status of p53. Teroxirone caused transient elevation of p53 that activates downstream p21 and procaspase-3 cleavage. The presence of caspase-3 inhibitor reverted apoptotic phenotype. Furthermore, we showed the cytotoxicity of teroxirone in H1299 cells with stable ectopic expression of p53, but not those of mutant p53. A siRNA-mediated knockdown of p53 expression attenuated drug sensitivity. The in vivo experiments demonstrated that teroxirone suppressed growth of xenograft tumors in nude mice. Being a potential therapeutic agent by restraining cell growth through apoptotic death at low concentrations, teroxirone provides a feasible perspective in reversing tumorigenic phenotype of human lung cancer cells.
authors: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors: Jing-Ping
authors: JP
authors: Wang
authors: Kai-Han
authors: KH
authors: Lin
authors: Chun-Yen
authors: CY
authors: Liu
authors: Ya-Chu
authors: YC
authors: Yu
authors: Pei-Tsun
authors: PT
authors: Wu
authors: Chien-Chih
authors: CC
authors: Chiu
authors: Chun-Li
authors: CL
authors: Su
authors: Kwun-Min
authors: KM
authors: Chen
authors: Kang
authors: K
authors: Fang
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D045304:Cytochromes c / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D015536:Down-Regulation; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D034741:RNA, Small Interfering / Q000235:genetics; D014227:Triazines / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D017304:Annexin A5; D034741:RNA, Small Interfering; D014227:Triazines; D016159:Tumor Suppressor Protein p53; C028786:teroxirone; D045304:Cytochromes c; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: Apoptosis; Human non-small-cell-lung-cancer cells; Teroxirone; p53