A triazole-conjugated benzoxazone induces reactive oxygen species and promotes autophagic apoptosis in human lung cancer cells

Chang Heng Hsieh, Jing Ping Wang, Chien Chih Chiu, Chun Yen Liu, Ching Fa Yao, Kang Fang

Research output: Contribution to journalArticle

  • 2 Citations

Abstract

Numerous approaches suggested that compounds with conjugated triazole moieties or benzoxazone pharmacores are effective to antagonize proliferation of human tumors. The current study reported that a synthetic triazole-conjugated benzoxazone, 4-((5-benzyl-1H-1,2,3-triazol-3-yl)-methyl)-7-methoxy-2H-benzo[b][1,4]-oxazin-3(4H)-one (BTO), inhibited growth rates of human non-small cell lung cancer cells. The cytotoxicity can be enhanced with increasing drug concentrations. More evidence supported that the induced reactive oxygen species lead to ultimate apoptotic cell death by recruiting autophagy. The mechanistic pathway as elucidated involved tumor suppressor p53 activation and LC3-1 conversion followed by PARP and procaspase-3 cleavage. Autophagy inhibition reverted apoptotic death and restored cell viabilities. BTO suppressed the development of A549 cell xenograft tumors by activating autophagy and apoptosis simultaneously. As an efficient tumor growth inhibitor with relatively small molecular weight, BTO is a viable addition to the existing list of lung cancer treatment.

LanguageEnglish
JournalApoptosis
Volume23
Issue number1
DOIs
Publication statusPublished - 2018 Jan 1

Fingerprint

Triazoles
Tumors
Reactive Oxygen Species
Lung Neoplasms
Autophagy
Cells
Apoptosis
Neoplasms
Growth Inhibitors
Oncology
Cell death
Cytotoxicity
Heterografts
Non-Small Cell Lung Carcinoma
Caspase 3
Cell Survival
Cell Death
Molecular Weight
Chemical activation
Molecular weight

Keywords

  • Apoptosis
  • Autophagy
  • Human non-small-cell-lung-cancer cells
  • Triazole
  • Tumor suppressor

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Cancer Research

Cite this

A triazole-conjugated benzoxazone induces reactive oxygen species and promotes autophagic apoptosis in human lung cancer cells. / Hsieh, Chang Heng; Wang, Jing Ping; Chiu, Chien Chih; Liu, Chun Yen; Yao, Ching Fa; Fang, Kang.

In: Apoptosis, Vol. 23, No. 1, 01.01.2018.

Research output: Contribution to journalArticle

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