Yu Xiaoming, Zhong Jingtao, Yan Li, Li Jie, Wang Hui, Wen Yan, Zhao Yu
Department of Ophthalmology, Shandong Jiaotong Hospital, Jinan, Shandong 250031, P.R. China.
Department of General Surgery, Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.
Int J Mol Med. 2016 Sep;38(3):861-8. doi: 10.3892/ijmm.2016.2676. Epub 2016 Jul 13.
Curcumin, a naturally occurring polyphenolic compound present in turmeric (Curcuma longa), exerts antitumor effects in various types of malignancy. However, the precise mechanisms responsible for the effects of curcumin on retinoblastoma (RB) cells have not been fully explored. In the present study, the molecular mechanisms by which curcumin exerts its anticancer effects in RB Y79 cells were investigated. The results showed that curcumin reduced cell viability in Y79 cells. Curcumin induced G1 phase arrest through downregulating the expression of cyclin D3 and cyclin-dependent kinase (CDK)2/6 and upregulating the expression of CDK inhibitor proteins p21 and p27. Curcumin-induced apoptosis of Y79 cells occurred through the activation of caspases-9/-3. Moreover, flow cytometric analysis showed that curcumin induced mitochondrial membrane potential (∆Ψm) collapse in Y79 cells. We also found that curcumin induced the phosphorylation of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK). JNK and p38 MAPK inhibitors significantly suppressed curcumin‑induced activation of caspases-9/-3 and inhibited the apoptosis of Y79 cells. Taken together, our results suggest that curcumin induced the apoptosis of Y79 cells through the activation of JNK and p38 MAPK pathways. These findings provide a novel treatment strategy for human RB.
姜黄素是姜黄（Curcuma longa）中天然存在的多酚化合物，对多种恶性肿瘤具有抗肿瘤作用。然而，姜黄素对视网膜母细胞瘤（RB）细胞作用的精确机制尚未完全阐明。在本研究中，我们研究了姜黄素在RB Y79细胞中发挥抗癌作用的分子机制。结果表明，姜黄素降低了Y79细胞的活力。姜黄素通过下调细胞周期蛋白D3和细胞周期蛋白依赖性激酶（CDK）2/6的表达以及上调CDK抑制蛋白p21和p27的表达来诱导G1期阻滞。姜黄素诱导的Y79细胞凋亡是通过激活半胱天冬酶-9/-3发生的。此外，流式细胞术分析表明，姜黄素诱导Y79细胞线粒体膜电位（∆Ψm）崩溃。我们还发现姜黄素诱导c-Jun氨基末端激酶（JNK）和p38丝裂原活化蛋白激酶（MAPK）磷酸化。JNK和p38 MAPK抑制剂显著抑制姜黄素诱导的半胱天冬酶-9/-3激活，并抑制Y79细胞凋亡。综上所述，我们的结果表明姜黄素通过激活JNK和p38 MAPK途径诱导Y79细胞凋亡。这些发现为人类RB提供了一种新的治疗策略。
