Functional characterization of HIC, a P2Y1 agonist, as a p53 stabilizer for prostate cancer cell death induction

Hien Thi Thu Le, Akshaya Murugesan, Nuno R Candeias, Olli Yli-Harja, Meenakshisundaram Kandhavelu

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Background: (1-(2-hydroxy-5-nitrophenyl)(4-hydroxyphenyl)methyl)indoline-4-carbonitrile (HIC), an agonist of the P2Y1 receptor (P2Y1R), induces cell death in prostate cancer cells. However, the molecular mechanism behind the inhibition of HIC in prostate cancer remains elusive. Methods and results: Here, to outline the inhibitory role of HIC on prostate cancer cells, PC-3 and DU145 cell lines were treated with the respective IC50 concentrations, which reduced cell proliferation, adherence properties and spheroid formation. HIC was able to arrest the cell cycle at G1/S phase and also induced apoptosis and DNA damage, validated by gene expression profiling. HIC inhibited the prostate cancer cells' migration and invasion, revealing its antimetastatic ability. P2Y1R-targeted HIC affects p53, MAPK and NF-κB protein expression, thereby improving the p53 stabilization essential for G1/S arrest and cell death. Conclusion: These findings provide an insight on the potential use of HIC, which remains the mainstay treatment for prostate cancer.

Original languageEnglish
Pages (from-to)1845-1864
Number of pages20
JournalFUTURE MEDICINAL CHEMISTRY
Volume13
Issue number21
Early online date10 Sep 2021
DOIs
Publication statusPublished - Nov 2021
Publication typeA1 Journal article-refereed

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  • Publication forum level 1

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