Teroxirone inhibited growth of human non-small cell lung cancer cells by activating p53

Jing Ping Wang, Kai Han Lin, Chun Yen Liu, Ya Chu Yu, Pei Tsun Wu, Chien Chih Chiu, Chun Li Su, Kwun Min Chen, Kang Fang

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)110-120
Number of pages11
JournalToxicology and Applied Pharmacology
Volume273
Issue number1
DOIs
Publication statusPublished - 2013 Nov 15

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Keywords

  • Apoptosis
  • Human non-small-cell-lung-cancer cells
  • P53
  • Teroxirone

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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