Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, Egypt.
Cancer Biol Ther. 2009 Nov;8(22):2175-85. doi: 10.4161/cbt.8.22.9882. Epub 2009 Nov 22.
Identification of agents that are nontoxic but can delay onset and/or progression of breast cancer, which is the main leading cause of cancer-related deaths among women, is highly desirable. Garlic-derived organosulfur compounds (OSCs) have highly effective antitumor effects, but the mechanism has yet to be investigated. The aim of the present study was undertaken to examine the effect of diallyl trisulfide (DATS), a promising cancer chemopreventive constituent of garlic, on growth of two cell lines respectively, MCF-7 human breast cancer cells and nontumorigenic MCF-12a mammary epithelial cells. The effects of DATS were examined by MTT assay, clonogenic survival assay, ELISA based apoptotic assay, TUNEL assay, immunofluoresence staining, flow Cytometry, RT-PCR and western blot analysis. Garlic constituent diallyl trisulfide (DATS) suppresses viability of cultured MCF-7 and MCF-12a cells respectively by decreasing the percent of cells in G(2)/M and inducing apoptotic cell death. DATS-induced apoptosis was markedly elevated in MCF-7 cells compared with MCF-12a cells and this was correlated with elevated levels of cyclin B1. The results from semi-quantitative and real-time RT-PCR indicated that DATS-enhanced the expression levels of FAS and cyclin D1, but in contrast, downregulated the expression levels of Akt and Bcl-2. Furthermore, the DATS-induced apoptosis was correlated with induction of pro-apoptotic Bax protein and p53 protein expression was upregulated and translocation to nucleus in MCF-7 cells. Together, the results of the present study show, for the first time, that DATS administration might offer a novel strategy for the treatment of human breast cancer.
寻找非毒性但能延迟乳腺癌发病和/或进展的药物是非常需要的，乳腺癌是导致女性癌症相关死亡的主要原因。大蒜衍生的有机硫化合物（OSCs）具有高效的抗肿瘤作用，但作用机制尚未得到研究。本研究旨在研究二烯丙基三硫化物（DATS），大蒜中一种有前途的癌症化学预防成分，对两种细胞系，即 MCF-7 人乳腺癌细胞和非致瘤性 MCF-12a 乳腺上皮细胞的生长的影响。通过 MTT 分析、集落形成存活分析、基于 ELISA 的凋亡分析、TUNEL 分析、免疫荧光染色、流式细胞术、RT-PCR 和 Western blot 分析来检测 DATS 的作用。大蒜成分二烯丙基三硫化物（DATS）通过降低 G2/M 期细胞的百分比并诱导凋亡性细胞死亡，分别抑制培养的 MCF-7 和 MCF-12a 细胞的活力。与 MCF-12a 细胞相比，DATS 诱导的 MCF-7 细胞凋亡明显增加，这与细胞周期蛋白 B1 水平升高有关。半定量和实时 RT-PCR 的结果表明，DATS 增强了 Fas 和细胞周期蛋白 D1 的表达水平，但相反，下调了 Akt 和 Bcl-2 的表达水平。此外，DATS 诱导的细胞凋亡与促凋亡 Bax 蛋白的诱导相关，p53 蛋白表达上调并在 MCF-7 细胞中转位到核内。总之，本研究首次表明，DATS 的给药可能为人类乳腺癌的治疗提供一种新策略。
