Jo Hong Jae, Song Ju Dong, Kim Kang Mi, Cho Yong Hoon, Kim Ki Hyung, Park Young Chul
Department of General Surgery, Medical Research Institute, Pusan National University School of Medicine, Busan 602-739, South Korea.
Oncol Rep. 2008 Jan;19(1):275-80.
Diallyl disulfide (DADS), a major organosulfur compound of garlic oil, is known to have an anticancer effect on human cancer cells. However, the exact mechanisms of this anticancer activity remain unclear. Here, we investigate the effects of DADS on cell cycle progression in human colon cancer HCT-116 cells by exploring the role played by regulatory molecules such as p53 and cyclin B1. Treatment of HCT-116 cells by DADS induced a marked growth inhibition with a slight reduction in viability and induced transient cell cycle arrest in the G2/M phase. Cyclin B1 is thought to play an important role in this process, as the DADS-induced G2/M phase arrest occurs with the increase of cyclin B1 expression. DADS also significantly induced the expression of p53, which contributes to cell cycle arrest in cancer cells, at a late time-point of 24 h. In addition, knockdown of p53 by siRNA did not affect cell cycle arrest, its reversibility, or the expression of cyclin B1 in the G2/M phase induced by DADS. Based on these results we conclude that, with the dynamic expression of cyclin B1, DADS induces reversible cell cycle arrest in the G2/M phase of HCT-116 cells through a p53-independent mechanism.
二烯丙基二硫化物（DADS）是大蒜油中的一种主要有机硫化合物，已知对人类癌细胞具有抗癌作用。然而，这种抗癌活性的确切机制仍不清楚。在此，我们通过探究p53和细胞周期蛋白B1等调控分子所起的作用，研究了DADS对人结肠癌HCT - 116细胞细胞周期进程的影响。用DADS处理HCT - 116细胞可诱导明显的生长抑制，细胞活力略有降低，并诱导细胞在G2/M期短暂停滞。细胞周期蛋白B1被认为在此过程中起重要作用，因为DADS诱导的G2/M期停滞伴随着细胞周期蛋白B1表达的增加。DADS在24小时的后期还显著诱导了p53的表达，p53有助于癌细胞的细胞周期停滞。此外，用小干扰RNA（siRNA）敲低p53并不影响细胞周期停滞、其可逆性或DADS诱导的G2/M期细胞周期蛋白B1的表达。基于这些结果，我们得出结论，随着细胞周期蛋白B1的动态表达，DADS通过一种不依赖p53的机制在HCT - 116细胞的G2/M期诱导可逆的细胞周期停滞。
