An increase in reactive oxygen species by deregulation of ARNT enhances chemotherapeutic drug-induced cancer cell death

Jiunn Min Shieh, Chih Jie Shen, Wei Chiao Chang, Hung Chi Cheng, Ya Yi Chan, Wan Chen Huang, Wen Chang Chang, Ben Kuen Chen

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Background: Unique characteristics of tumor microenvironments can be used as targets of cancer therapy. The aryl hydrocarbon receptor nuclear translocator (ARNT) is an important mediator of tumor progression. However, the functional role of ARNT in chemotherapeutic drug-treated cancer remains unclear. Methodology/Principal Findings: Here, we found that knockdown of ARNT in cancer cells reduced the proliferation rate and the transformation ability of those cells. Moreover, cisplatin-induced cell apoptosis was enhanced in ARNT-deficient cells. Expression of ARNT also decreased in the presence of cisplatin through proteasomal degradation pathway. However, ARNT level was maintained in cisplatin-treated drug-resistant cells, which prevented cell from apoptosis. Interestingly, reactive oxygen species (ROS) dramatically increased when ARNT was knocked down in cancer cells, enhancing cisplatin-induced apoptosis. ROS promoted cell death was inhibited in cells treated with the ROS scavenger, N-acetyl-cysteine (NAC). Conclusions/Significance: These results suggested that the anticancer activity of cisplatin is attributable to its induction of the production of ROS by ARNT degradation. Targeting ARNT could be a potential strategy to eliminate drug resistance in cancer cells.

Original languageEnglish
Article numbere99242
JournalPloS one
Volume9
Issue number6
DOIs
Publication statusPublished - 2014 Jun 12

All Science Journal Classification (ASJC) codes

  • General

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