二烯丙基二硫化物通过p53/p21和MEK-ERK途径诱导人食管鳞状细胞癌G2/M期阻滞并促进细胞凋亡。
Diallyl disulfide induces G2/M arrest and promotes apoptosis through the p53/p21 and MEK-ERK pathways in human esophageal squamous cell carcinoma.
作者信息
Yin Xiaoran, Zhang Rong, Feng Cheng, Zhang Jun, Liu Dong, Xu Kun, Wang Xijing, Zhang Shuqun, Li Zongfang, Liu Xinlian, Ma Hongbing
机构信息
Department of Oncology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.
Department of Gastroenterology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China.
出版信息
Oncol Rep. 2014 Oct;32(4):1748-56. doi: 10.3892/or.2014.3361. Epub 2014 Jul 25.
Esophageal squamous cell carcinoma (ESCC) is an aggressive tumor with high incidence and mortality worldwide. Diallyl disulfide (DADS) is a natural organosulfur compound, isolated from garlic. In this study, MTT assay showed that DADS significantly reduced cell viability in a dose- and time-dependent manner in ESCC cells, with lower toxicity in normal liver cells. Cell cycle analysis revealed that DADS made G2/M phase arrest. Molecular analysis suggested that this cell cycle arrest was likely made by the decrease of cyclin B1, cdc2, p-cdc2, cdc25c in concomitance with activation of the p53/p21 pathway. Apoptosis was detected by Annexin V/PI staining. The molecule markers showed that DADS induced apoptosis through activating caspases, altering the Bax/Bcl-2 balance and suppressing the MEK-ERK pathway. Our data indicated that DADS has the potential to be an effective and safe anticancer agent for ESCC therapy in the near future.
食管鳞状细胞癌（ESCC）是一种侵袭性肿瘤，在全球范围内发病率和死亡率都很高。二烯丙基二硫化物（DADS）是一种从大蒜中分离出来的天然有机硫化合物。在本研究中，MTT 法显示 DADS 以剂量和时间依赖性方式显著降低 ESCC 细胞的活力，对正常肝细胞的毒性较低。细胞周期分析表明 DADS 使细胞停滞于 G2/M 期。分子分析表明，这种细胞周期停滞可能是由于细胞周期蛋白 B1、细胞周期蛋白依赖性激酶 2（cdc2）、磷酸化 cdc2（p-cdc2）、细胞周期蛋白依赖性激酶 25C（cdc25c）减少，同时 p53/p21 通路激活所致。通过 Annexin V/PI 染色检测细胞凋亡。分子标志物表明 DADS 通过激活半胱天冬酶、改变 Bax/Bcl-2 平衡和抑制 MEK-ERK 通路诱导细胞凋亡。我们的数据表明，在不久的将来，DADS 有可能成为一种有效且安全的用于 ESCC 治疗的抗癌药物。
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