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Butyrate inhibits HBV replication and HBV‐induced hepatoma cell proliferation via modulating SIRT‐1/Ac‐p53 regulatory axis
Author(s) -
Pant Kishor,
Mishra Amit K.,
Pradhan Saman Man,
Nayak Baibaswata,
Das Prasenjit,
Shalimar Dr,
Saraya Anoop,
Venugopal Senthil K.
Publication year - 2019
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22946
Subject(s) - biology , butyrate , hbx , sodium butyrate , cell growth , viral replication , cancer research , hepatitis b virus , microbiology and biotechnology , telomerase , apoptosis , virology , cell culture , virus , biochemistry , genetics , fermentation , gene
Butyrate, a histone deacetylase inhibitor, has several therapeutic applications, including cancer. However, the effect of butyrate in HBV replication is not known so far. It was hypothesized that butyrate might inhibit HBV replication and host cell proliferation via SIRT‐1. It was found that the increased expression of SIRT‐1 in Hep G2.2.15 cells (HBV expressing cells) than Hep G2 cells. Next the expression of SIRT‐1 and Acetylated p53 (Ac‐p53) were measured in the liver biopsy samples of chronic hepatitis B (CHB) patients with high viral load and compared to CHB patients with low viral load and found that there was a high SIRT‐1 expression and a low Ac‐p53 levels in CHB patients with high viral load compared to CHB patients with low viral load. Incubation of butyrate inhibited SIRT‐1 expression and cell proliferation. Inhibition of SIRT‐1 by butyrate or SIRT‐1 siRNA increased the levels of Ac‐p53. The elevated Ac‐p53 decreased p‐akt, cyclin D1, and thereby inhibited cell proliferation. Incubation of butyrate with Hep G2.2.15 cells also inhibited HBx protein expression, HBV‐DNA and hepatitis B surface antigen (HBsAg). Taken together, the data showed that butyrate inhibited HBV replication and cell proliferation by inhibiting SIRT‐1 expression in hepatoma cells.