Sodium butyrate induces cell death by autophagy and reactivates a tumor suppressor gene DIRAS1 in renal cell carcinoma cell line UOK146
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Sodium butyrate (SB), a histone deacetylase inhibitor, is emerging as a potent anti-cancer drug for different types of cancers. In the present study, anti-cancer activity of SB in Xp11.2 (TFE3) translocated renal cell carcinoma cell line UOK146 was studied. Anti-proliferative effect of SB in renal cell carcinoma (RCC) cell line UOK146 was evaluated by MTT assay and morphological characteristics were observed by phase contrast microscopy which displayed the cell death after SB treatment. SB induces DNA fragmentation and change in nuclear morphology observed by increased sub-G1 region cell population and nuclear blebbings. Cell cycle arrest at G2/M phase was found after SB treatment. UOK146 cell line shows autophagy mode of cell death as displayed by acridine orange staining and flow cytometry analysis. LC3-II, a protein marker of autophagy, was also found to be upregulated after SB treatment. A tumor suppressor gene DIRAS1 was upregulated after SB treatment, displaying its anti-cancer potential at molecular level. These findings suggest that SB could serve as a novel regulator of tumor suppressors and lead to the discovery of novel therapeutics with better and enhanced anti-cancer activity.
KeywordsSodium butyrate UOK146 Renal cell carcinoma Autophagy DIRAS1
We acknowledge W M Linehan, National Cancer Institute, USA, for providing the UOK146 cell line. DBT-BHU Interdisciplinary School of Life Sciences (ISLS) Banaras Hindu University, Varanasi, India, for Flow Cytometry and Real Time PCR facilities. Prof. Prasenjit Guchhait, Regional Centre for Biotechnology, Faridabad, India, for anti-LC3 antibody. The Indian Council of Medical Research (ICMR), Government of India, New Delhi, for fellowship support of JRF and SRF to Shiv Prakash Verma.
Compliance with ethical standards
The authors declare that they have no competing interests.
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