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

Liang Wei
Ying Mu
Lina Ji
Xin Guo
Tongyi Li


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