title: Butyrate induces ROS-mediated apoptosis by modulating miR-22/SIRT-1 pathway in hepatic cancer cells.
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.
authors.affiliation: Faculty of Life Sciences and Biotechnology, South Asian University, Chanakyapuri, New Delhi, India.
authors.forename: Kishor
authors.initials: K
authors.lastname: Pant
authors.affiliation: Faculty of Life Sciences and Biotechnology, South Asian University, Chanakyapuri, New Delhi, India.
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Yadav
authors.affiliation: Faculty of Life Sciences and Biotechnology, South Asian University, Chanakyapuri, New Delhi, India.
authors.forename: Parul
authors.initials: P
authors.lastname: Gupta
authors.affiliation: Faculty of Life Sciences and Biotechnology, South Asian University, Chanakyapuri, New Delhi, India.
authors.forename: Rakibul
authors.initials: R
authors.lastname: Islam
authors.affiliation: Department of Gastroenterology and Human Nutrition Unit, All India Institute of Medical Sciences, New Delhi, India.
authors.forename: Anoop
authors.initials: A
authors.lastname: Saraya
authors.affiliation: Faculty of Life Sciences and Biotechnology, South Asian University, Chanakyapuri, New Delhi, India. Electronic address: drsenthil@sau.ac.in.
authors.forename: Senthil K
authors.initials: SK
authors.lastname: Venugopal
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D020148:Butyric Acid / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; C548375:MIRN22 microRNA, human; D035683:MicroRNAs; D017382:Reactive Oxygen Species; D020148:Butyric Acid; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: Apoptosis; Cell proliferation; Hepatocellular carcinoma; Non-alcoholic fatty liver disease; Short chain fatty acid