Department of Surgery, China Medical University Beigang Hospital, Yunlin 651, Taiwan.
Environ Toxicol. 2013 Sep;28(9):479-88. doi: 10.1002/tox.20737. Epub 2011 Jun 21.
Diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS) are major organosulfur compounds exiting in garlic (Allium sativum). These compounds are reported to exhibit various pharmacological properties such as antibacteria, antiangiogenesis, anticancer, and anticoagulation, and they also induce cytotoxicity and induction of apoptosis in human cancer cells. Although these compounds show wide spectrum of biological activities, there are no reports to show that DAS, DADS, and DATS affected migration and invasion of human colon cancer cells, and their exact molecular mechanisms are not well investigated. Therefore, the purpose of this study was to determine whether DAS, DADS, and DATS affected the invasion and migration abilities of colo 205 human colon cancer cells. The results indicate that DAS, DADS, and DATS at 10 and 25 μM inhibited the migration and invasion of colo 205 cells in the order of DATS < DADS < DAS. DATS is the highest for inhibition of migration and invasion of colo 205 cells. DAS, DADS, and DATS induce downregulation expression of PI3K, Ras, MEKK3, MKK7, ERK1/2, JNK1/2, and p38 and then lead to the inhibition of MMP-2, -7, and -9. DAS, DADS, and DATS inhibited NF-κB and COX-2 for leading to the inhibition of cell proliferation. Taken together, these results demonstrated that application of DAS, DADS, and DATS might serve as potential antimetastatic drugs.
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)是大蒜(Allium sativum)中存在的主要有机硫化合物。这些化合物被报道具有多种药理活性,如抗菌、抗血管生成、抗癌和抗凝作用,它们还能诱导人癌细胞的细胞毒性和细胞凋亡。尽管这些化合物表现出广泛的生物活性,但没有报道表明 DAS、DADS 和 DATS 影响人结肠癌细胞的迁移和侵袭,其确切的分子机制也未得到很好的研究。因此,本研究旨在确定 DAS、DADS 和 DATS 是否影响 colo 205 人结肠癌细胞的侵袭和迁移能力。结果表明,DAS、DADS 和 DATS 在 10 和 25 μM 时按 DATS < DADS < DAS 的顺序抑制了 colo 205 细胞的迁移和侵袭。DATS 对抑制 colo 205 细胞的迁移和侵袭作用最强。DAS、DADS 和 DATS 诱导 PI3K、Ras、MEKK3、MKK7、ERK1/2、JNK1/2 和 p38 的下调表达,从而抑制 MMP-2、-7 和 -9。DAS、DADS 和 DATS 抑制 NF-κB 和 COX-2 导致细胞增殖受到抑制。总之,这些结果表明,DAS、DADS 和 DATS 的应用可能作为潜在的抗转移药物。