Graduate Institute of Food Science and Technology, National Taiwan University, No 1, Sec 4, Roosevelt Road, Taipei 106, Taiwan.
J Agric Food Chem. 2010 Jun 9;58(11):7096-103. doi: 10.1021/jf100613x.
Diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS), extracted from crushed garlic by steam-distillation, have been reported to provide the anticancer activity in several cancer types. However, their mechanisms of effects on skin cancer cells remain unclear. Therefore, we used human melanoma A375 cells and basal cell carcinoma cells as the models to elucidate the effects of these three allyl sulfides. Basal cell carcinoma (BCC) is known to be the most prevalent type of skin cancer, and melanoma is the most lethal form. We found that DATS revealed better growth inhibition of A375 and BCC cells than DADS and DAS did. We further demonstrated that DATS increased intracellular reactive oxygen species (ROS) generation, induced cytosolic Ca(2+) mobilization, and decreased mitochondrial membrane potential (DeltaPsim). Western blot results showed the concordance for the expression of molecules involved in G(2)/M arrest and apoptosis observed by cell cycle and cell viability analysis. Moreover, we detected the activation of p53 pathway in response to the oxidative DNA damage. DATS also displayed selective target of growth inhibition between skin cancer cells and normal keratinocyte HaCaT cells. Taken together, these results suggest that DATS is a potential anticancer compound for skin cancer.
二烯丙基二硫醚（DAS）、二烯丙基三硫醚（DATS）和二烯丙基二硫醚（DADS），由水蒸气蒸馏从粉碎的大蒜中提取，已被报道在几种癌症类型中具有抗癌活性。然而，它们对皮肤癌细胞的作用机制尚不清楚。因此，我们使用人黑色素瘤 A375 细胞和基底细胞癌细胞作为模型，阐明这三种烯丙基硫醚的作用。基底细胞癌（BCC）是最常见的皮肤癌类型，黑色素瘤是最致命的形式。我们发现 DATS 对 A375 和 BCC 细胞的生长抑制作用优于 DADS 和 DAS。我们进一步证明 DATS 增加了细胞内活性氧（ROS）的产生，诱导了细胞质 Ca(2+)动员，并降低了线粒体膜电位（DeltaPsim）。Western blot 结果表明，细胞周期和细胞活力分析观察到的参与 G(2)/M 期阻滞和细胞凋亡的分子表达一致。此外，我们检测到 p53 通路对氧化 DNA 损伤的激活。DATS 对皮肤癌细胞和正常角质形成细胞 HaCaT 细胞的生长抑制也具有选择性的靶向作用。综上所述，这些结果表明 DATS 是一种潜在的皮肤癌抗癌化合物。
