Cheng Ya-Min, Tsai Ching-Chou, Hsu Yi-Chiang
Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan.
Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan.
Int J Mol Sci. 2016 Sep 12;17(9):1530. doi: 10.3390/ijms17091530.
Globally, cervical cancer is the most common malignancy affecting women. The main treatment methods for this type of cancer include conization or hysterectomy procedures. Sulforaphane (SFN) is a natural, compound-based drug derived from dietary isothiocyanates which has previously been shown to possess potent anti-tumor and chemopreventive effects against several types of cancer. The present study investigated the effects of SFN on anti-proliferation and G₂/M phase cell cycle arrest in cervical cancer cell lines (Cx, CxWJ, and HeLa). We found that cytotoxicity is associated with an accumulation of cells in the G₂/M phases of the cell-cycle. Treatment with SFN led to cell cycle arrest as well as the down-regulation of Cyclin B1 expression, but not of CDC2 expression. In addition, the effects of GADD45β gene activation in cell cycle arrest increase proportionally with the dose of SFN; however, mitotic delay and the inhibition of proliferation both depend on the dosage of SFN used to treat cancer cells. These results indicate that SFN may delay the development of cancer by arresting cell growth in the G₂/M phase via down-regulation of Cyclin B1 gene expression, dissociation of the cyclin B1/CDC2 complex, and up-regulation of GADD45β proteins.
在全球范围内，宫颈癌是影响女性的最常见恶性肿瘤。这类癌症的主要治疗方法包括锥切术或子宫切除术。萝卜硫素（SFN）是一种源自膳食异硫氰酸盐的天然化合物类药物，此前已证明其对多种类型的癌症具有强大的抗肿瘤和化学预防作用。本研究调查了SFN对宫颈癌细胞系（Cx、CxWJ和HeLa）的抗增殖作用及G₂/M期细胞周期阻滞的影响。我们发现细胞毒性与细胞周期G₂/M期细胞的积累有关。用SFN处理导致细胞周期阻滞以及细胞周期蛋白B1表达下调，但细胞周期蛋白依赖性激酶2（CDC2）表达未下调。此外，生长停滞和DNA损伤诱导蛋白45β（GADD45β）基因激活在细胞周期阻滞中的作用随SFN剂量成比例增加；然而，有丝分裂延迟和增殖抑制均取决于用于处理癌细胞的SFN剂量。这些结果表明，SFN可能通过下调细胞周期蛋白B1基因表达、解离细胞周期蛋白B1/CDC2复合物以及上调GADD45β蛋白，使细胞生长停滞在G₂/M期，从而延缓癌症的发展。
