Abstract
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.
Highlights
Gastric cancer is one of the leading causes of death of cancer patients and is the most common type of malignancy in Chinese Academy of Science (China) [1]
We have previously reported that diallyl disulfide (DADS) inhibited the growth of gastric cancer in vitro and in vivo [9,10], and that it induced cell cycle G2/M arrest in human gastric cancer MGC803 cells [19]
The results indicated that the proliferation of BGC823 cells was significantly reduced by treatment with DADS for 96 h in a dose-dependent manner
Summary
Gastric cancer is one of the leading causes of death of cancer patients and is the most common type of malignancy in China [1]. Its diallyl disulfide (DADS) content, has become a quite appealing anti-carcinogenic agent. This is due, in part, to its ability to induce apoptosis in vitro [4] and to inhibit the formation and growth of tumors in vivo [5,6]. DADS has been shown to inhibit the in vitro and in vivo growth of breast, liver, lung, gastric, colon, and prostate cancers, as well as neuroblastoma and leukemia cell lines [5,7,8,9,10,11,12,13,14]. DADS may be a useful therapeutic tool for the prevention of environmentally induced cancers
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