Sodium butyrate induces cell death by autophagy and reactivates a tumor suppressor gene DIRAS1 in renal cell carcinoma cell line UOK146

Abstract

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.

SCFA: mechanisms and functional importance in the gut

“…This is explained by a metabolic shift occurring in cancerous cells using preferentially glucose as the energy source. The inhibition of cell proliferation is generally characterised by an increase in reactive oxygen species production, DNA damages and cell cycle arrest, suggesting that SCFA initiate apoptosis signalling in cancer cells (93–96) . Indeed, through the activation of the pro-apoptotic protein BAX, the upregulation of apoptosis-inducing factor-mitochondria associated 1 isoform 6 and the reduction of mitochondrial membrane potential, SCFA stimulate the cytochrome c release which drives caspase 3 activation (93) .…”

<p>Sodium Butyrate Selectively Kills Cancer Cells and Inhibits Migration in Colorectal Cancer by Targeting Thioredoxin-1</p>

“…[8][9][10] NaB has been found to inhibit cell proliferation and migration of colorectal cancer, promote CRC cell apoptosis and induce autophagy and cell death. [10][11][12][13][14] The previously reported the correlation between NaB and Oxidative stress. 15 Numerous studies have shown that NaB significantly induces reactive oxygen species (ROS)mediated apoptosis in a variety of cancers.…”

Mitochondrial E3 ubiquitin ligase 1 promotes autophagy flux to suppress the development of clear cell renal cell carcinomas

“…Our previous study found that microtubule‐associated protein family 1 (MAP1S) can promote autophagy clearance of lipid droplets and reduce DNA double‐strand breaks and genome instability, consequently suppressing the development of ccRCC and promoting patient survival . Similarly, other groups have shown that autophagy can suppress ccRCC development . Therefore, whether autophagy promotes or inhibits cancer development or whether autophagy has different regulatory mechanisms for cancer development in different tissues requires further investigation …”

“…19 Similarly, other groups have shown that autophagy can suppress ccRCC development. [20][21][22] Therefore, whether autophagy promotes or inhibits cancer development or whether autophagy has different regulatory mechanisms for cancer development in different tissues requires further investigation. 9,23 Mitochondrial E3 ubiquitin ligase 1 (Mul1), a multifunctional mitochondrial membrane-associated protein located on the outer membrane of the mitochondrion with two transmembrane domains and one Ring-finger domain, 24 regulates different biological processes such as mitochondrial dynamics, cell growth, apoptosis and mitophagy (autophagy degradation of mitochondria), through ubiquitination and SUMOylation.…”