Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Down-regulation of F-actin and paxillin by N-(3-(1H-tetrazol-1-yl)phenyl) isonicotinamide derivative inhibits proliferation of prostate cancer cells

Liang Wei¹, Ying Mu¹, Lina Ji² , Xin Guo², Tongyi Li¹

¹Department of Urology, First Hospital of Shanxi Medical University; ²Department of Medical Oncology, Shanxi Bethune Hospital, Taiyuan, Shanxi 030032, China.

For correspondence:- Lina Ji Email: JoyceBryanpml@yahoo.com Tel:+8613277652399

Accepted: 22 June 2020 Published: 31 July 2020

Citation: Wei L, Mu Y, Ji L, Guo X, Li T. Down-regulation of F-actin and paxillin by N-(3-(1H-tetrazol-1-yl)phenyl) isonicotinamide derivative inhibits proliferation of prostate cancer cells. Trop J Pharm Res 2020; 19(7):1389-1395 doi: 10.4314/tjpr.v19i7.8

© 2020 The authors.
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Abstract

Purpose: To investigate the effect of N-(3-(1H-tetrazol-1-yl)phenyl) isonicotinamide derivative (TPIN) on prostate cancer cells, and the mechanism involved.

Methods: The cytotoxicity of TPIN in DU145 and PC3 cells was determined using Cell Counting Kit-8, while apoptosis induction was assayed by flow cytometry using Annexin V?fluorescein isothiocyanate dye. Changes in expressions of F?actin, RAC-α and paxillin were determined by western blot assay.

Results: Cell proliferation was effectively inhibited by TPIN in the concentration range of 0.75-15 µM. The values of half-minimum inhibitory concentration (IC₅₀) of TPIN for DU145 and PC3 cells at 48 h were 5.6 and 10.2 µM, respectively (p < 0.05). Treatment with 5.6 µM TPIN increased apoptosis to 59.64 % in DU145 cells, and 54.21% in PC3 cells. Cleaved caspase-3 and caspase-9 levels were increased by TPIN treatment in both cell lines (p < 0.05). Moreover, the levels of F?actin and paxillin were significantly downregulated by TPIN treatment in DU145 and PC3 cells (p < 0.05). In TPIN-treated DU145 and PC3 cells, cofilin?1expression was up-regulated, relative to control cells.

Conclusion: TPIN exhibits cytotoxic effect on prostate cancer cells via activation of apoptosis. It elevates cofilin?1 and the expressions of targets F?actin and paxillin in prostate cancer cells. Thus, TPIN is a potential chemotherapeutic agent for prostate cancer. However, further investigations, including clinical trials are required to authenticate these findings.

Keywords: Prostate cancer, F?actin, Paxillin, Apoptosis, Caspases