Molecular Biology Laboratory, Zoology Department, Faculty of Science, Sohag University, Sohag, Egypt.
Nutr Cancer. 2012;64(8):1251-60. doi: 10.1080/01635581.2012.721156.
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.
大蒜的健康益处已被流行病学和实验研究证明。二烯丙基二硫化物(DADS),是大蒜油中发现的主要有机硫化合物,已知可降低体外和体内乳腺癌的发病率。这里报道的研究表明,DADS 通过干扰细胞周期生长阶段,增加亚 G0 群体并显著停止 DNA 合成,从而诱导 MCF-7 乳腺癌细胞系凋亡。DADS 还诱导磷脂酰丝氨酸从质膜的内叶到外叶转移,并激活半胱天冬酶-3。进一步的研究表明,DADS 以剂量依赖的方式调节细胞中 Bax、Bcl-2、Bcl-xL 和 Bcl-w 的水平,表明 Bcl-2 家族蛋白参与了 DADS 诱导的细胞凋亡。组蛋白去乙酰化酶抑制剂(HDACi)被认为可抑制肿瘤生长并诱导癌细胞凋亡。这里表明,DADS 在 MCF-7 细胞中具有 HDACi 特性,因为它降低了从乙酰化底物上去除乙酰基的速度,并诱导组蛋白-4(H4)过度乙酰化。因此,数据表明 DADS 的 HDACi 特性可能负责诱导乳腺癌细胞凋亡。