双去甲氧基姜黄素通过诱导 ROS 积累和调节衰老相关通路来抑制 MCF-7 细胞的增殖。
Bisdemethoxycurcumin suppresses MCF-7 cells proliferation by inducing ROS accumulation and modulating senescence-related pathways.
机构信息
Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Taipa, Macao 999078, China.
出版信息
Pharmacol Rep. 2013;65(3):700-9. doi: 10.1016/s1734-1140(13)71048-x.
BACKGROUND
Bisdemethoxycurcumin (BDMC) is a natural derivative of curcumin present in the phenolic components extracted from the dried rhizome of Curcuma longa L. BDMC demonstrated potential chemotherapeutic activities but the underlying mechanisms have not been fully clarified. In the present study, the role of reactive oxidative species (ROS) in the anti-cancer effects of BDMC was investigated.
METHODS
MCF-7 cells were exposed to BDMC, and then the cell proliferation, colony formation ability and cell cycle profile were analyzed. Cellular ROS level was determined by flow cytometry and fluorescent microscope observation using specific fluorescent probes. Mitochondrial membrane potential (ψm) was assessed using JC-1. In addition, effects of BDMC on senescence-related molecules were analyzed by western blot assay.
RESULTS
BDMC significantly inhibited MCF-7 breast cancer cell proliferation, while a rapid rise of the intracellular ROS level accompanied with a reduction of Dym were observed. In addition, BDMC activated the pro-apoptotic protein p53 and its downstream effector p21 as well as the cell cycle regulatory proteins p16 and its downstream effector retinoblastoma protein (Rb). All of these BDMC-induced effects were counteracted with the pre-incubation of the antioxidant N-acetylcysteine (NAC).
CONCLUSIONS
These results suggested that BDMC-induced ROS accumulation may contribute to its inhibitory effect on MCF-7 cell viability through regulation of p53/p21 and p16/Rb pathways.
背景
双去甲氧基姜黄素（BDMC）是姜黄素的一种天然衍生物，存在于姜黄干燥根茎中提取的酚类成分中。BDMC 表现出潜在的化疗活性，但作用机制尚未完全阐明。在本研究中，研究了活性氧（ROS）在 BDMC 抗癌作用中的作用。
方法
将 MCF-7 细胞暴露于 BDMC 中，然后分析细胞增殖、集落形成能力和细胞周期谱。通过流式细胞术和使用特定荧光探针的荧光显微镜观察来测定细胞内 ROS 水平。使用 JC-1 评估线粒体膜电位（ψm）。此外，通过 Western blot 分析测定 BDMC 对衰老相关分子的影响。
结果
BDMC 显著抑制 MCF-7 乳腺癌细胞增殖，同时观察到细胞内 ROS 水平迅速升高，Dym 降低。此外，BDMC 激活了促凋亡蛋白 p53 及其下游效应蛋白 p21 以及细胞周期调节蛋白 p16 及其下游效应蛋白视网膜母细胞瘤蛋白（Rb）。所有这些 BDMC 诱导的作用都被抗氧化剂 N-乙酰半胱氨酸（NAC）的预孵育所抵消。
结论
这些结果表明，BDMC 诱导的 ROS 积累可能通过调节 p53/p21 和 p16/Rb 途径，有助于其对 MCF-7 细胞活力的抑制作用。
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