Regulation of tNOX expression through the ROS-p53-POU3F2 axis contributes to cellular responses against oxaliplatin in human colon cancer cells

Journal of Experimental & Clinical Cancer Research : CR
Huei-Yu ChenPin Ju Chueh

Abstract

Oxaliplatin belongs to the platinum-based drug family and has shown promise in treating cancer by binding to DNA to induce cytotoxicity. However, individual patients show diverse therapeutic responses toward oxaliplatin due to yet-unknown underlying mechanisms. We recently established that oxaliplatin also exert its anti-cancer activity in gastric cancer cell lines by targeting tumor-associated NADH oxidase (tNOX), attenuate NAD+ generation and reduce NAD+-dependent sirtuin 1 (SIRT1) deacetylase activity, which in turn enhances p53 acetylation and apoptosis. In this study, differential cellular outcomes in response to oxaliplatin exposure of p53-wild-type versus p53-null HCT116 human colon cancer cells were examined. Cell growth profile was determined by cell impedance measurements and apoptosis was analyzed by flow cytometry. The engagement between oxaliplatin and tNOX protein was studied by cellular thermal shift assay. Furthermore, western blot analysis revealed that p53 was important in regulating tNOX expression in these cell lines. In p53-wild-type cells, we found that oxaliplatin inhibited cell growth by inducing apoptosis and concurrently down-regulating tNOX at both the transcriptional and translational levels. In p53-...Continue Reading

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Citations

Feb 12, 2020·Development·Angela ChuiSong-Hai Shi
Nov 9, 2019·Journal of Experimental & Clinical Cancer Research : CR·You ZouShi-Ming Chen
Dec 24, 2018·Journal of Experimental & Clinical Cancer Research : CR·Yongxin QiuZhihong Jiang
Mar 15, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Xufeng WangZhenggang Zhu

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Methods Mentioned

BETA
acetylation
transfection
PCR
Assay
thermal shift
electrophoresis
flow cytometry
thermal melting

Software Mentioned

CETSA

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