Loss of butyrate-induced apoptosis in human hepatoma cell lines HCC-M and HCC-T having substantial Bcl-2 expression

Abstract

We have demonstrated that sodium butyrate induces differentiation in human hepatoma cells; however, recent studies have shown that this agent causes apoptosis in some types of cancer cells. In this study, we examined whether sodium butyrate causes apoptosis in the human hepatoma cell lines, HCC-M and HCC-T. The growth of human hepatoma cells was dose-dependently reduced by sodium butyrate. Flow cytometric analysis showed cell-cycle arrest at the G 1 phase in the sodium butyrate-treated cells. Apoptotic change was never found in treated cells at concentration levels of less than 5 mmol/L. Sodium butyrate decreased p53 expression and increased p21 WAF-1 expression in HCC-T and HCC-M cells having the wild-type p53 gene. Western blot analysis showed that Bcl-2 was expressed in the HCC-T and HCC-M cells, and its expression was increased after exposure to sodium butyrate. Antisense oligodeoxynucleotide against bcl-2 easily caused apoptosis. These results indicate that sodium butyrate hardly induces apoptotic change in the human hepatoma cell lines, HCC-T and HCC-M, with the increase of Bcl-2 expression. Cellcycle arrest in the G 1 phase caused by sodium butyrate was suggested to be induced by the increase in p21 WAF-1 expression, but this change did not link with the p53 increase.

Sodium butyrate enhances Fas-mediated apoptosis of human hepatoma cells

“…The gene for p21 was also up-regulated in the present study. p21 is a potent inhibitor of cyclin-dependent kinases whose expression was enhanced by SB in other studies [21,25,26]. Moreover, we revealed that Bik and Bak are increased, and c-FLIP L decreased, by Western blotting.…”

Acquisition of Resistance to Butyrate Enhances Survival after Stress and Induces Malignancy of Human Colon Carcinoma Cells

“…In vitro studies using different colorectal cell lines have demonstrated that butyrate is able to inhibit cell proliferation, induce cell differentiation and apoptosis, and enhance immunosurveillance and anti-inflammatory responses (6,7,13,22,33). However, the molecular bases of the chemopreventive effects of butyrate remain largely unknown.…”

“…Butyrate inhibits cell proliferation and induces differentiation and first apoptosis in transformed cells from colon and other tissues (5)(6)(7). It first imposes cell cycle arrest (8,9), afterward triggering a differentiation program reflected in changes in specific markers such as alkaline phosphatase (ALP) activity, which can subsequently induce cells to undergo apoptosis.…”

An Update on the Other Telomerase Inhibitors: Non-G-Quadruplex Interactive Agent, Non-Antisense, Non-Reverse Transcriptase Telomerase Inhibitors

“…It acts as a histone deacetylase inhibitor [49][50][51]. When added to four human hepatocellular carcinoma cell lines, sodium butyrate reduced cell proliferation without inducing apoptosis [52].…”