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Tropical Journal of Pharmaceutical Research

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N-(4-hydroxyphenyl) retinamide inhibits migration of renal carcinoma cells and promotes autophagy via MAPK p38 pathway

Jianguo Gao, Jianer Tang, Yu Chen, Junwen Shen, Ning Wang, Zhihai Fang, Guiqin Shen, Fan Ren, Rongjiang Wang

Abstract


Purpose: To investigate the effect of N-(4-hydroxyphenyl) retinamide (4HPR) on autophagy and migration of renal carcinoma cells.
Methods: Renal cancer cell lines were treated with various concentrations of 4HPR. Proliferation of the cells was studied using 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltrazolium bromide (MTT), while apoptosis and cell cycle arrest were determined by flow cytometry.
Results: Treatment of RCCs with 30 μM 4HPR caused significant inhibition of viability. In 786-O and OS-RC-2 cell lines, 4HPR reduced colony formation by 39 and 43 %, respectively. In addition, 4HPR increased the percentage of 786-O cells in G1 phase from 58.79 ± 3.43 to 71.68 ± 4.47 % (p < 0.05). It also decreased the percentage of cells in the S-phase from 21.98 ± 2.78 to 09.17 ± 1.43 %, and enhanced the activation of p38 and JNK in 786-O cells at 48 h. Western blot assay showed that the activation of p38 and JNK by 4HPR was inhibited on pre-treatment with SB203580 (inhibitor of p38) and SP600125 (inhibitor of JNK), respectively. Reduction of 786-O cell viability by 4HPR treatment was also significantly inhibited by pre-treatment with sp203580 and sp600125 (p < 0.05). Furthermore, the inhibitors also reversed the effect of 4HPR on the expressions of Bax and Bcl-2 in 786-O cells.
Conclusion: These results indicate that 4HPR inhibits the growth of renal cancer cells via activation of MAPK signalling pathway. Thus, 4HPR is a potential drug target for management of renal cancer.

Keywords: Retinamide, Renal cancer, Autophagy, MAPK signalling, Cell proliferation, N-terminal kinase




http://dx.doi.org/10.4314/tjpr.v17i6.4
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