Biochemistry & Pharmacology: Open Access
Open Access

Abstract

Diallyl Disulfide Increases Histone Acetylation and P21^WAF1 Expression in Human Gastric Cancer Cells In vivo and In vitro

Bo Su, Shu Lin Xiang, Jian Su, Hai Ling Tang, Qiang Jin Liao, Yu Juan Zhou and Su Qi

Diallyl disulfide (DADS) exerts numerous anticancer effects, involving multiple molecular mechanisms. In particular, DADS has been revealed as a potential inhibitor attenuating histone deacetylase (HDAC) activity, which could aid cancer prevention and therapy by inducing histone hyperacetylation and consequently reactivating epigenetically silenced tumor suppressor genes involved in cancer initiation and progression. In an in vitro study, we demonstrated that DADS increased histones H3 and H4 acetylation in human gastric cancer MGC803 cells in a time-dependent fashion, accompanied by increased p21WAF1 protein levels, which was consistent with G2/M phase cell cycle arrest. DADS
also demonstrated dose-dependent antitumor effects in MGC803-xenografted nude mice in vivo, resulting in tumor cells growth inhibition and G2/M phase arrest. Acetylated histones H3 and H4 were up-regulated by administration of DADS in association with elevated p21WAF1 protein expression. There was no evidence of gross toxicity associated with DADS treatment. DADS also preferentially enhanced acetylation of histone H3 relative to histone H4 both in vivo and in vitro. In addition, characteristic features of cell differentiation were observed in xenografted tumor cells. These results suggest that DADS can cause cell cycle arrest and inhibit cell proliferation by inducing hyperacetylation of histones
H3 and H4 and increasing p21WAF1 expression in MGC803 cells, which may partly account for its antitumor effects in gastric cancer. These results indicate that DADS may be useful for gastric cancer prevention, and may have important implications for epigenetic therapy by virtue of its ability to modulate histone acetylation.