An Increase in Reactive Oxygen Species by Deregulation of ARNT Enhances Chemotherapeutic Drug-Induced Cancer Cell Death

doi:10.1371/journal.pone.0099242

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Title:	An Increase in Reactive Oxygen Species by Deregulation of ARNT Enhances Chemotherapeutic Drug-Induced Cancer Cell Death
Authors:	Shieh, Jiunn-Min Shen, Chih-Jie Chang, Wei-Chiao Cheng, Hung-Chi Chan, Ya-Yi Huang, Wan-Chen Chang, Wen-Chang Chen, Ben-Kuen
Contributors:	通識教育中心
Keywords:	RECEPTOR NUCLEAR TRANSLOCATOR TRANSCRIPTION FACTOR GENE-EXPRESSION APOPTOSIS ACTIVATION STRESS AHR DOXORUBICIN RESPONSES MDR1
Date:	2014-06
Issue Date:	2015-05-06 21:18:33 (UTC+8)
Publisher:	Public Library Science
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.
Relation:	Plos One, v.9 n.6, e99242
Appears in Collections:	[The Center For General Education] Periodical Articles

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