skip to main content

SciTech ConnectSciTech Connect

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

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. - Highlights: • Teroxirone repressed tumor cell growth in nude mice of human lung cancer cells. • The apoptotic cell death reverted by caspase-3 inhibitor is related to p53 status. • Teroxirone provides a good candidate for lung cancer treatment.
Authors:
; ; ; ;  [1] ;  [2] ;  [3] ;  [4] ;  [1]
  1. Department of Life Science, National Taiwan Normal University, Taipei, Taiwan (China)
  2. Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan (China)
  3. Department of Human Development and Family Studies, National Taiwan Normal University, Taipei, Taiwan (China)
  4. Department of Chemistry, National Taiwan Normal University, Taipei, Taiwan (China)
Publication Date:
OSTI Identifier:
22285493
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 273; Journal Issue: 1; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; CONCENTRATION RATIO; DNA DAMAGES; EPOXIDES; GROWTH; IN VITRO; IN VIVO; LUNGS; MICE; NEOPLASMS; TOXICITY; TUMOR CELLS