Diallyl Disulfide-Induced Apoptosis in a Breast-Cancer Cell Line (MCF-7) May Be Caused by Inhibition of Histone Deacetylation

Abstract

The health benefits of garlic have been proven by epidemiological and experimental studies. Diallyl disulphide (DADS), the major organosulfur compound found in garlic oil, is known to lower the incidence of breast cancer both in vitro and in vivo. The studies reported here demonstrate that DADS induces apoptosis in the MCF-7 breast-cancer cell line through interfering with cell-cycle growth phases in a way that increases the sub-G₀ population and substantially halts DNA synthesis. DADS also induces phosphatidylserine translocation from the inner to the outer leaflet of the plasma membrane and activates caspase-3. Further studies revealed that DADS modulates the cellular levels of Bax, Bcl-2, Bcl-xL, and Bcl-w in a dose-dependent manner, suggesting the involvement of Bcl-2 family proteins in DADS induced apoptosis. Histone deacetylation inhibitors (HDACi) are known to suppress cancer growth and induce apoptosis in cancer cells. Here it is shown that DADS has HDACi properties in MCF-7 cells as it lowers the removal of an acetyl group from an acetylated substrate and induces histone-4 (H4) hyper-acetylation. The data thus indicate that the HDACi properties of DADS may be responsible for the induction of apoptosis in breast cancer cells.

ACKNOWLEDGMENTS

This work was supported by Zoology Department, Faculty of Science Sohag University, Egypt. We would like to thank Professor M. F. El-Sayed for helping providing chemicals and kits necessary to accomplish this study.

Abbreviations

DADSDiallyl disulphide

DMSODimethylsulfoxide

FBSFetal bovine serum

HDACHistone deacetylation

HDACiHistone deacetylation inhibitor

PBSPhosphate buffered saline

PIPropidium iodide

PSphosphatidylserine

RIPARadio-Immuno Precipitation Assay

RTRoom temperature

TSATrichostatin A