Sodium butyrate-induced DAPK-mediated apoptosis in human gastric cancer cells
Hyunsoo Shin1, Yeo Song Lee, Yong Chan Lee
1Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.
Abstract:
Epigenetic mechanisms of histone acetylation/deacetylation play an important role in the regulation of gene expression associated with the cell cycle and apoptosis. Recently, sodium butyrate, a histone deacetylase (HDAC) inhibitor, has been shown to exhibit anticancer effects via differentiation and apoptosis of cancer cells. Sodium butyrate may be a potential anticancer chemotherapeutic drug; however, the precise mechanism underlying the anticancer effects of sodium butyrate has not been clearly elucidated. In the present study, we investigated the role of death-associated protein kinase (DAPK) on the apoptosis of human gastric cancer cells induced by sodium butyrate. We observed that sodium butyrate induced apoptosis in human gastric cancer cells. Treatment with the HDAC inhibitor sodium butyrate increased the expression of caspase-3 and DAPK1/2 genes but decreased the expression of Bcl-2 in human gastric cancer cells. The expression of DAPK3, p53 and p21 were not altered by sodium butyrate treatment. Analysis of the general expression patterns revealed that sodium butyrate increased the expression of DAPK1/2 but decreased the expression of FAK and induced changes in the proliferation of apoptosis-related genes in human gastric cancer cells. These data suggest that DAPK expression prompts apoptosis by reducing the FAK protein level in sodium butyrate-induced apoptosis of human gastric cancer cells.
Insights
Sodium butyrate, a histone deacetylase (HDAC) inhibitor, induces apoptosis in human gastric cancer cells. This anticancer effect involves increased death-associated protein kinase (DAPK) expression, which prompts apoptosis by reducing FAK protein levels.
Area of Science:
- Molecular Biology
- Cancer Research
- Epigenetics
Background:
- Histone acetylation/deacetylation are key epigenetic regulators of gene expression in cell cycle and apoptosis.
- Sodium butyrate, a histone deacetylase (HDAC) inhibitor, demonstrates anticancer potential through cancer cell differentiation and apoptosis.
- The precise mechanisms of sodium butyrate's anticancer effects, particularly its role in apoptosis, require further elucidation.
Purpose of the Study:
- To investigate the role of death-associated protein kinase (DAPK) in sodium butyrate-induced apoptosis of human gastric cancer cells.
- To elucidate the molecular mechanisms underlying sodium butyrate's anticancer effects in gastric cancer.
Main Methods:
- Human gastric cancer cells were treated with sodium butyrate.
- Gene expression levels of apoptosis-related proteins (caspase-3, Bcl-2, DAPK1/2, DAPK3, p53, p21, FAK) were analyzed.
- Changes in proliferation and apoptosis-related gene expression patterns were assessed.
Main Results:
- Sodium butyrate treatment induced apoptosis in human gastric cancer cells.
- HDAC inhibition by sodium butyrate increased caspase-3 and DAPK1/2 gene expression while decreasing Bcl-2 expression.
- Sodium butyrate increased DAPK1/2 expression, decreased FAK expression, and altered other apoptosis-related gene expressions.
Conclusions:
- DAPK expression plays a crucial role in promoting apoptosis in sodium butyrate-treated human gastric cancer cells.
- The mechanism involves DAPK-mediated reduction of FAK protein levels, contributing to sodium butyrate-induced apoptosis.
- Sodium butyrate shows promise as an anticancer agent, with DAPK and FAK as key molecular players in its apoptotic pathway.
