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-G(0) 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.

Diallyl disulfide induces G2/M arrest and promotes apoptosis through the p53/p21 and MEK-ERK pathways in human esophageal squamous cell carcinoma

“…Apoptosis induction involves different apoptotic genes and enzymes depending on the cell type of different tumors (16). DADS has the ability to induce apoptosis of human tumor cells including those of colon, gastric, prostate and breast origin (10,11,18,(20)(21)(22). Our study confirmed the apoptotic effects of DADS on ECA109 cells by using several methods.…”

Effects of Garlic Oil on Pancreatic Cancer Cells

“…Evidence showed that DADS and DATS suppress the growth of multiple cancer types both in vitro and in vivo (Powolny and Singh, 2008;Herman-Antosiewicz et al, 2010;Lee et al, 2011;Altonsy and Andrews, 2011;Altonsy et al, 2012;Wang et al, 2012). Further study would be necessary to confirm that in the following experiments.…”

PTEN activation through K163 acetylation by inhibiting HDAC6 contributes to tumour inhibition

“…31,32 Inhibitors of HDACs, particularly classical HDACs, can induce the reexpression of silenced genes, cell growth arrest and apoptosis in various cancer cell lines. [33][34][35][36][37][38] As such, HDAC inhibitors function as promising anti-cancer agents. Suberoylanilide hydroxamic acid (SAHA) is the first HDAC inhibitor approved by the U.S. Food and Drug Administration for treatment of cutaneous T-cell lymphoma.…”