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
Highlights
Renal cell carcinoma (RCC), a neoplasm in majority of adult kidneys, is a tumour of epithelial origin [1,2]
The effect of 4HPR on viability of renal carcinoma cells was investigated at concentrations of 5, 10, 15, 20, 25 and 30 μM by MTT assay
The present study investigated the effect of 4HPR on renal carcinoma cell proliferation, apoptosis and migration with the aim of developing novel strategy for efficient treatment of renal carcinoma
Summary
Renal cell carcinoma (RCC), a neoplasm in majority of adult kidneys, is a tumour of epithelial origin [1,2]. The cells were treated with 5, 10, 15, 20, 25 and 30 μM of 4HPR, or with medium alone (control) for 48 h, and seeded at a density of 1 x 105 cells per well in 96-well plates which were incubated in DMEM medium containing 10 % FBS at 37 oC in an atmosphere of 5 % CO2. The 786-O cells were seeded at a density of 2 x 106 cells per well in 6-well plates and incubated with 4HPR either in DMEM or in medium alone (control) for 48 h. The cells were seeded into 6-well plates at a density of 2 x 106 cells per well and incubated with 4HPR either in DMEM medium or in medium alone (control) for 48 h.
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