Diallyl trisulfide selectively causes Bax- and Bak-mediated apoptosis in human lung cancer cells.
Diallyl trisulfide selectively causes Bax- and Bak-mediated apoptosis in human lung cancer cells.
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DOI：
10.1002/em.20431
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发表时间：
2009-04
影响因子：
2.8
通讯作者：
Singh, Shivendra V.
中科院分区：
文献类型：
--
作者：
Xiao, Dong;Zeng, Yan;Hahm, Eun-Ryeong;Kim, Young-Ae;Ramalingam, Suresh;Singh, Shivendra V.
大蒜衍生的有机硫化合物（OSCs）在动物模型中对化学诱导的肺癌具有非常有效的保护作用。我们现在证明大蒜成分二烯丙基三硫化物（DATS）通过引起G2-M期细胞周期阻滞和凋亡细胞死亡，抑制培养的人肺癌细胞系H358（一种非小细胞肺癌细胞系）和H460（一种大细胞肺癌细胞系）的活力。另一方面，正常人支气管上皮细胞系BEAS-2B对DATS的生长抑制和诱导凋亡的抗性明显高于肺癌细胞。我们还发现，即使盐盐结构的细微变化也会对其生物活性产生重大影响。例如，DATS明显比二烯丙基硫醚或二烯丙基二硫醚更有效地抑制肺癌细胞的增殖。dats介导的G2-M期细胞周期阻滞是通过下调周期蛋白依赖性激酶1 （Cdk1）和细胞分裂周期25C蛋白表达导致Tyr15磷酸化（无活性）Cdk1的积累来解释的。dats诱导的肺癌细胞凋亡与促凋亡蛋白Bax、Bak和BID的诱导相关，与抗凋亡蛋白Bcl-2和Bcl-xL的表达降低相关，而与BEAS-2B无关。敲低Bax和Bak蛋白对dats诱导的凋亡细胞质组蛋白相关DNA断裂具有显著的保护作用。另一方面，在dats诱导的细胞凋亡中，BID蛋白是不可缺少的。综上所述，本研究提示Bax和Bak蛋白是dats诱导的人肺癌细胞凋亡的关键靶点。
Garlic-derived organosulfur compounds (OSCs) are highly effective in affording protection against chemically-induced pulmonary carcinogenesis in animal models. We now demonstrate that garlic constituent diallyl trisulfide (DATS) suppresses viability of cultured human lung cancer cell lines H358 (a non-small cell lung cancer cell line) and H460 (a large cell lung cancer cell line) by causing G2-M phase cell cycle arrest and apoptotic cell death. On the other hand, a normal human bronchial epithelial cell line BEAS-2B was significantly more resistant to growth inhibition and apoptosis induction by DATS compared with lung cancer cells. We also found that even a subtle change in the OSC structure could have a significant impact on its biological activity. For example, DATS was significantly more effective than either diallyl sulfide or diallyl disulfide against proliferation of lung cancer cells. The DATS-mediated G2-M phase cell cycle arrest was explained by down-regulation of cyclin-dependent kinase 1 (Cdk1) and cell division cycle 25C protein expression leading to accumulation of Tyr15 phosphorylated (inactive) Cdk1. The DATS-induced apoptosis correlated with induction of proapoptotic proteins Bax, Bak, and BID, and a decrease in the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL in lung cancer cells but not in BEAS-2B. Knockdown of Bax and Bak proteins conferred significant protection against DATS-induced apoptotic cytoplasmic histone-associated DNA fragmentation. On the other hand, BID protein was dispensable for DATS-induced apoptosis. In conclusion, the present study indicates that Bax and Bak proteins are critical targets of DATS-induced apoptosis in human lung cancer cells.
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影响因子：
11.2
作者：
Antosiewicz, Jedrzej;Herman-Antosiewicz, Anna;Singh, Shivendra V.
通讯作者：
Singh, Shivendra V.
影响因子：
11.5
作者：
Hahm, Eun-Ryeong;Arlotti, Julie A.;Singh, Shivendra V.
通讯作者：
Singh, Shivendra V.
影响因子：
82.9
作者：
LeBlanc, H;Lawrence, D;Ashkenazi, A
通讯作者：
Ashkenazi, A
影响因子：
4.1
作者：
BRADY, JF;ISHIZAKI, H;YANG, CS
通讯作者：
YANG, CS
影响因子：
11.2
作者：
Choi, S;Singh, SV
通讯作者：
Singh, SV