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Peroxiporins are induced upon oxidative stress insult and are associated with oxidative stress resistance in colon cancer cell lines

Čipak Gašparović, Ana; Milković, Lidija; Rodrigues, Claudia; Mlinarić, Monika; Soveral, Graça (2021) Peroxiporins are induced upon oxidative stress insult and are associated with oxidative stress resistance in colon cancer cell lines. Antioxidants, 10 (11). ISSN 2076-3921

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Abstract

Oxidative stress can induce genetic instability and change cellular processes, resulting in colorectal cancer. Additionally, adaptation of oxidative defense causes therapy resistance, a major obstacle in successful cancer treatment. Peroxiporins are aquaporin membrane channels that facilitate H2O2 membrane permeation, crucial for regulating cell proliferation and antioxidative defense. Here, we investigated four colon cancer cell lines (Caco-2, HT-29, SW620, and HCT 116) for their sensitivity to H2O2, cellular antioxidative status, and ROS intracellular accumulation after H2O2 treatment. The expression of peroxiporins AQP1, AQP3, and AQP5 and levels of NRF2, the antioxidant transcription factor, and PPARγ, a transcription factor that regulates lipid metabolism, were evaluated before and after oxidative insult. Of the four tested cell lines, HT-29 was the most resistant and showed the highest expression of all tested peroxiporins and the lowest levels of intracellular ROS, without differences in GSH levels, catalase activity, nor NF2 and PPARγ levels. Caco-2 shows high expression of AQP3 and similar resistance as HT-29. These results imply that oxidative stress resistance can be obtained by several mechanisms other than the antioxidant defense system. Regulation of intracellular ROS through modulation of peroxiporin expression may represent an additional strategy to target the therapy resistance of cancer cells.

Item Type: Article
Uncontrolled Keywords: aquaporin ; colon cancer cell line ; oxidative stress ; NRF2
Subjects: BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences
Divisions: Division of Molecular Medicine
Depositing User: Ana Čipak Gašparović
Date Deposited: 04 Jan 2022 10:43
URI: http://fulir.irb.hr/id/eprint/6866
DOI: 10.3390/antiox10111856

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