Butyrate induces ROS-mediated apoptosis by modulating miR-22/SIRT-1 pathway in hepatic cancer cells

Kishor Pant, Ajay K. Yadav, Parul Gupta, Rakibul Islam, Anoop Saraya, Senthil K. Venugopal

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

Butyrate is one of the short chain fatty acids, produced by the gut microbiota during anaerobic fermentation of dietary fibres. It has been shown that it can inhibit tumor progression via suppressing histone deacetylase and can induce apoptosis in cancer cells. However, the comprehensive pathway by which butyrate mediates apoptosis and growth arrest in cancer cells still remains unclear. In this study, the role of miR-22 in butyrate-mediated ROS release and induction of apoptosis was determined in hepatic cells. Intracellular expression of miR-22 was increased when the Huh 7 cells were incubated with sodium butyrate. Over-expression of miR-22 or addition of sodium butyrate inhibited SIRT-1 expression and enhanced the ROS production. Incubation of cells with anti-miR-22 reversed the effects of butyrate. Butyrate induced apoptosis via ROS production, cytochrome c release and activation of caspase-3, whereas addition of N-acetyl cysteine or anti-miR-22 reversed these butyrate-induced effects. Furthermore, sodium butyrate inhibited cell growth and proliferation, whereas anti-miR-22 inhibited these butyrate-mediated changes. The expression of PTEN and gsk-3 was found to be increased while p-akt and β-catenin expression was decreased significantly by butyrate. These data showed that butyrate modulated both apoptosis and proliferation via miR-22 expression in hepatic cells.

Original languageEnglish (US)
Pages (from-to)340-349
Number of pages10
JournalRedox Biology
Volume12
DOIs
StatePublished - Aug 1 2017

Keywords

  • Apoptosis
  • Cell proliferation
  • Hepatocellular carcinoma
  • Non-alcoholic fatty liver disease
  • Short chain fatty acid

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry

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