Seki Taiichiro, Hosono Takashi, Hosono-Fukao Tomomi, Inada Kahoru, Tanaka Rie, Ogihara Jun, Ariga Toyohiko
Laboratory of Nutrition and Physiology, Department of Applied Life Sciences, Nihon University Graduate School of Bioresource Sciences, Kameino 1866, Fujisawa, Kanagawa 252-8510, Japan.
Asia Pac J Clin Nutr. 2008;17 Suppl 1:249-52.
Alk(en)yl sulfides are characteristic flavor components of garlic. Several lines of epidemiological study indicate that the risk of a certain cancer can be prevented by consumption of garlic. In this manuscript, we examined the anticancer property of garlic-derived alk(en)yl sulfides, and the molecular basis especially for diallyl trisulfide which is a major constituent of the garlic oil. Alk(en)yl sulfides with different numbers of sulfur atom (i.e., mono-, di-, and trisulfide) were synthesized and purified (>99%). The anticancer activity of the alk(en)yl sulfides was primarily examined using human colon cancer cells HCT-15 and DLD-1. The growth of the cells was significantly suppressed by diallyl trisulfide, but neither diallyl monosulfide nor diallyl disulfide showed such an effect. The number of cells arrested at G2/M phase, the cells with a sub-G1 DNA content, and the cells with caspase-3 activity were dramatically increased by diallyl trisulfide treatment. Diallyl trisulfide disrupted microtubule network formation of the cells, and microtubule fragments could be seen at the interphase. There was a specific oxidative modification of cysteine residues Cys12 beta and Cys354 beta, forming S-allylmercaptocysteines in the tubulin molecule. These results suggest that diallyl trisulfide is responsible, at least in part, for the epidemiologically proven anticancer effect for garlic eaters.
烯基硫化物是大蒜的特征性风味成分。多项流行病学研究表明，食用大蒜可预防某种癌症的风险。在本论文中，我们研究了大蒜衍生的烯基硫化物的抗癌特性，尤其是大蒜油的主要成分二烯丙基三硫化物的分子基础。合成并纯化了具有不同硫原子数的烯基硫化物（即单硫化物、二硫化物和三硫化物）（纯度>99%）。主要使用人结肠癌细胞HCT-15和DLD-1检测烯基硫化物的抗癌活性。二烯丙基三硫化物显著抑制了细胞的生长，但二烯丙基单硫化物和二烯丙基二硫化物均未显示出这种效果。经二烯丙基三硫化物处理后，停滞在G2/M期的细胞数量、DNA含量低于G1期的细胞数量以及具有半胱天冬酶-3活性的细胞数量显著增加。二烯丙基三硫化物破坏了细胞的微管网络形成，在间期可见微管片段。微管蛋白分子中的半胱氨酸残基Cys12β和Cys354β发生了特定的氧化修饰，形成了S-烯丙基巯基半胱氨酸。这些结果表明，二烯丙基三硫化物至少部分地解释了食用大蒜在流行病学上已得到证实的抗癌作用。
