Allyl Sulfides Inhibit Cell Growth of Skin Cancer Cells through Induction of DNA Damage Mediated G2/M Arrest and Apoptosis
Allyl Sulfides Inhibit Cell Growth of Skin Cancer Cells through Induction of DNA Damage Mediated G2/M Arrest and Apoptosis
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DOI：
10.1021/jf100613x
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发表时间：
2010-06-09
影响因子：
6.1
通讯作者：
Sheen, Lee-Yan
中科院分区：
文献类型：
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作者：
Wang, Hsiao-Chi;Yang, Jen-Hung;Sheen, Lee-Yan
通过蒸汽蒸馏从粉碎的大蒜中提取的二烯丙基硫醚（DAS）、二烯丙基二硫醚（DADS）和二烯丙基三硫醚（DATS），据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仍不清楚。因此，我们用人黑素瘤A375细胞和基底细胞癌细胞作为模型来阐明这三种烯丙基硫醚的作用。基底细胞癌（BCC）是已知的最常见的皮肤癌类型，而黑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比DADS和DAS更好。我们进一步证明DATS增加了细胞内活性氧（ROS）的产生，诱导了胞质Ca2 +动员，并降低了线粒体膜电位（ΔΨm）。蛋白质印迹结果显示，细胞周期和细胞活力分析所观察到的参与G(2)/M期阻滞和凋亡的分子表达具有一致性。此外，我们检测到针对氧化性DNA损伤的p53通路的激活。DATS在皮肤癌细胞和正常角质形成细胞HaCaT细胞之间也显示出选择性的生长抑制靶点。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。
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 Ca2+ mobilization, and decreased mitochondrial membrane potential (Delta Psi m). 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.