Cancer Research Institute, University of South China, Hengyang, Hunan, China.
Braz J Med Biol Res. 2010 Mar;43(3):271-8. doi: 10.1590/s0100-879x2010007500004.
Diallyl disulfide (DADS) inhibits growth and induces cell cycle G2/M arrest in human gastric cancer MGC803 cells. In this study, 15 mg/L DADS exerted similar effects on growth and cell cycle arrest in human gastric cancer BGC823 cells. Due to the importance of cell cycle redistribution in DADS-mediated anti-carcinogenic effects, we investigated the role of checkpoint kinases (Chk1 and Chk2) during DADS-induced cell cycle arrest. We hypothesized that DADS could mediate G2/M phase arrest through either Chk1 or Chk2 signal transduction pathways. We demonstrated that DADS induced the accumulation of phosphorylated Chk1, but not of Chk2, and that DADS down-regulated Cdc25C and cyclin B1. The expression of mRNA and total protein for Chkl and Chk2 was unchanged. Chk1 is specifically phosphorylated by ATR (ATM-RAD3-related gene). Western blot analysis showed that phospho-ATR was activated by DADS. Taken together, these data suggest that cell cycle G2/M arrest, which was associated with accumulation of the phosphorylated forms of Chk1, but not of Chk2, was involved in the growth inhibition induced by DADS in the human gastric cancer cell line BGC823. Furthermore, the DADS-induced G2/M checkpoint response is mediated by Chk1 signaling through ATR/Chk1/Cdc25C/cyclin B1, and is independent of Chk2.
二烯丙基二硫（DADS）抑制人胃癌 MGC803 细胞的生长并诱导细胞周期 G2/M 期阻滞。在本研究中，15mg/L 的 DADS 对人胃癌 BGC823 细胞的生长和细胞周期阻滞具有相似的作用。由于细胞周期重分布在 DADS 介导的抗癌作用中非常重要，我们研究了检查点激酶（Chk1 和 Chk2）在 DADS 诱导的细胞周期阻滞中的作用。我们假设 DADS 可以通过 Chk1 或 Chk2 信号转导途径介导 G2/M 期阻滞。我们证明 DADS 诱导磷酸化 Chk1 的积累，但不诱导 Chk2 的积累，并且 DADS 下调 Cdc25C 和细胞周期蛋白 B1。Chkl 和 Chk2 的 mRNA 和总蛋白表达不变。Chk1 被 ATR（ATM-RAD3 相关基因）特异性磷酸化。Western blot 分析表明 DADS 激活了磷酸化 ATR。总之，这些数据表明，与 Chk1 的磷酸化形式的积累相关的细胞周期 G2/M 期阻滞参与了 DADS 诱导的人胃癌细胞系 BGC823 的生长抑制。此外，DADS 诱导的 G2/M 检查点反应是通过 ATR/Chk1/Cdc25C/细胞周期蛋白 B1 介导的 Chk1 信号转导，并且不依赖于 Chk2。
