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 - Jun 12 2014

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Aryl Hydrocarbon Receptor Nuclear Translocator
Deregulation
Cell death
hydrocarbons
cell death
reactive oxygen species
Reactive Oxygen Species
Cell Death
cisplatin
drugs
receptors
Cisplatin
Pharmaceutical Preparations
Neoplasms
neoplasms
apoptosis
Cells
cells
Apoptosis
Tumors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

An increase in reactive oxygen species by deregulation of ARNT enhances chemotherapeutic drug-induced cancer cell death. / Shieh, Jiunn Min; Shen, Chih Jie; Chang, Wei Chiao; Cheng, Hung Chi; Chan, Ya Yi; Huang, Wan Chen; Chang, Wen Chang; Chen, Ben Kuen.

In: PLoS One, Vol. 9, No. 6, e99242, 12.06.2014.

Research output: Contribution to journalArticle

Shieh, Jiunn Min ; Shen, Chih Jie ; Chang, Wei Chiao ; Cheng, Hung Chi ; Chan, Ya Yi ; Huang, Wan Chen ; Chang, Wen Chang ; Chen, Ben Kuen. / An increase in reactive oxygen species by deregulation of ARNT enhances chemotherapeutic drug-induced cancer cell death. In: PLoS One. 2014 ; Vol. 9, No. 6.
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AU - Huang, Wan Chen

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