Azoxystrobin induces apoptosis of human esophageal squamous cell carcinoma KYSE-150 cells through triggering of the mitochondrial pathway

Xiao Ke Shi, Xiao Bo Bian, Tao Huang, Bo Wen, Ling Zhao, Huai Xue Mu, Sarwat FATIMA, Bao Min Fan, Zhaoxiang BIAN, Lin Fang Huang, Cheng Yuan Lin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Recent studies indicate that mitochondrial pathways of apoptosis are potential chemotherapeutic target for the treatment of esophageal cancer. Azoxystrobin (AZOX), a methoxyacrylate derived from the naturally occurring strobilurins, is a known fungicide acting as a ubiquinol oxidation (Qo) inhibitor of mitochondrial respiratory complex III. In this study, the effects of AZOX on human esophageal squamous cell carcinoma KYSE-150 cells were examined and the underlying mechanisms were investigated. AZOX exhibited inhibitory effects on the proliferation of KYSE-150 cells with inhibitory concentration 50% (IC50) of 2.42 μg/ml by 48 h treatment. Flow cytometry assessment revealed that the inhibitory effect of AZOX on KYSE-150 cell proliferation occurred with cell cycle arrest at S phase and increased cell apoptosis in time-dependent and dose-dependent manners. Cleaved poly ADP ribose polymerase (PARP), caspase-3 and caspase-9 were increased significantly by AZOX. It is worth noted that the Bcl-2/Bax ratios were decreased because of the down-regulated Bcl-2 and up-regulated Bax expression level. Meanwhile, the cytochrome c release was increased by AZOX in KYSE-150 cells. AZOX-induced cytochrome c expression and caspase-3 activation was significantly blocked by Bax Channel Blocker. Intragastric administration of AZOX effectively decreased the tumor size generated by subcutaneous inoculation of KYSE-150 cells in nude mice. Consistently, decreased Bcl-2 expression, increased cytochrome c and PARP level, and activated caspase-3 and caspase-9 were observed in the tumor samples. These results indicate that AZOX can effectively induce esophageal cancer cell apoptosis through the mitochondrial pathways of apoptosis, suggesting AZOX or its derivatives may be developed as potential chemotherapeutic agents for the treatment of esophageal cancer.

Original languageEnglish
Article number277
JournalFrontiers in Pharmacology
Volume8
Issue numberMAY
DOIs
Publication statusPublished - 17 May 2017

Scopus Subject Areas

  • Pharmacology
  • Pharmacology (medical)

User-Defined Keywords

  • Anti-tumor
  • Apoptosis
  • Azoxystrobin
  • Human esophageal squamous cell carcinoma
  • Mitochondrial pathway

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