Carcinogenesis：大蒜抗肿瘤增殖机制

近来研究显示大蒜具有防治肿瘤和癌症的功效。大蒜中的锗和硒等元素可抑制肿瘤细胞和癌细胞的生长，早期实验发现，癌症发生率最低的人群就是血液中含硒量最高的人群。美国国家癌症组织认为，全世界最具抗癌潜力的植物中，位居榜首的是大蒜。

大蒜衍生的有机硫化合物（OSCS）包括硫化二烯丙基是众所周知的具有多种健康益处的化合物，最近的一项研究报告指出，由于其特有的选择性的抗增殖作用，在癌症的化学预防和治疗发面呈现了非常大的开发前景。

研究报告指出硫化二烯丙基能阻断早期有丝分裂，诱导细胞凋亡。但潜在的分子机制尚未完全阐明。研究数据显示多硫化二烯丙基(类)化合物作用于活性氧（ROS）和微管蛋白。微管解聚防止正常主轴微管的形成，从而导致G2/M停滞

研究数据表明多硫化二烯丙基(类)化合物可激活JNK，介导抗凋亡蛋白Bcl-2的磷酸化和下游蛋白质的表达，发挥抗肿瘤增殖功效。

doi:10.1093/carcin/bgs240
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Ros-Independent Jnk Activation and Multi-Site Phosphorylation of Bcl-2 Link Diallyl Tetrasulfide-Induced Mitotic Arrest to Apoptosis.

Kelkel M, Cerella C, Mack F, Schneider T, Jacob C, Schumacher M, Dicato M, Diederich M.

Garlic-derived organosulfur compounds (OSCs) including diallylpolysulfides are well known for various health-beneficial properties and recent reports even point to a potential role of diallylpolysulfides as chemopreventive and -therapeutic agents in cancer treatment due to their selective anti-proliferative effects. In this respect, diallyltri- and -tetrasulfide are reported as strong inducers of an early mitotic arrest and subsequent apoptosis, but the underlying molecular mechanisms and the link between these two events are not yet fully elucidated. Our data revealed that diallyltetrasulfide (DAS4) acts independently of reactive oxygen species (ROS) and tubulin represents one of its major cellular targets. Tubulin depolymerization prevents the formation of normal spindle microtubules thereby leading to G2/M arrest. Here, we provide evidence that JNK, which is activated early in response to DAS4 treatment, mediates multi-site phosphorylation and subsequent proteolysis of the anti-apoptotic protein Bcl-2. As the latter event occurs concomitantly with the onset of apoptosis and the chemical JNK inhibitor SP600125 not only prevented Bcl-2 phosphorylation and proteolysis but also apoptosis following DAS4 treatment, we suggest that these JNK-mediated modulations of Bcl-2 represent the missing link connecting early microtubule inactivation to the induction of apoptosis.