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, Kwunmin 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

Fingerprint

teroxirone
Non-Small Cell Lung Carcinoma
Cells
Growth
Cytotoxicity
Caspase 3
Phenotype
Caspase Inhibitors
Epoxy Compounds
Cell growth
Cell death
Heterografts
Nude Mice
Small Interfering RNA
DNA Damage
Tumors
Lung Neoplasms
Cell Death
Apoptosis
Derivatives

Keywords

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

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Cite this

Teroxirone inhibited growth of human non-small cell lung cancer cells by activating p53. / Wang, Jing Ping; Lin, Kai Han; Liu, Chun Yen; Yu, Ya Chu; Wu, Pei Tsun; Chiu, Chien Chih; Su, Chun-Li; Chen, Kwunmin; Fang, Kang.

In: Toxicology and Applied Pharmacology, Vol. 273, No. 1, 15.11.2013, p. 110-120.

Research output: Contribution to journalArticle

Wang, Jing Ping ; Lin, Kai Han ; Liu, Chun Yen ; Yu, Ya Chu ; Wu, Pei Tsun ; Chiu, Chien Chih ; Su, Chun-Li ; Chen, Kwunmin ; Fang, Kang. / Teroxirone inhibited growth of human non-small cell lung cancer cells by activating p53. In: Toxicology and Applied Pharmacology. 2013 ; Vol. 273, No. 1. pp. 110-120.
@article{8116387880c44e71af9850ca0beb3777,
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.",
keywords = "Apoptosis, Human non-small-cell-lung-cancer cells, P53, Teroxirone",
author = "Wang, {Jing Ping} and Lin, {Kai Han} and Liu, {Chun Yen} and Yu, {Ya Chu} and Wu, {Pei Tsun} and Chiu, {Chien Chih} and Chun-Li Su and Kwunmin Chen and Kang Fang",
year = "2013",
month = "11",
day = "15",
doi = "10.1016/j.taap.2013.08.007",
language = "English",
volume = "273",
pages = "110--120",
journal = "Toxicology and Applied Pharmacology",
issn = "0041-008X",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Teroxirone inhibited growth of human non-small cell lung cancer cells by activating p53

AU - Wang, Jing Ping

AU - Lin, Kai Han

AU - Liu, Chun Yen

AU - Yu, Ya Chu

AU - Wu, Pei Tsun

AU - Chiu, Chien Chih

AU - Su, Chun-Li

AU - Chen, Kwunmin

AU - Fang, Kang

PY - 2013/11/15

Y1 - 2013/11/15

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Human non-small-cell-lung-cancer cells

KW - P53

KW - Teroxirone

UR - http://www.scopus.com/inward/record.url?scp=84884705953&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84884705953&partnerID=8YFLogxK

U2 - 10.1016/j.taap.2013.08.007

DO - 10.1016/j.taap.2013.08.007

M3 - Article

C2 - 23954467

AN - SCOPUS:84884705953

VL - 273

SP - 110

EP - 120

JO - Toxicology and Applied Pharmacology

JF - Toxicology and Applied Pharmacology

SN - 0041-008X

IS - 1

ER -