Stereoisomers of Astaxanthin Inhibit Human Colon Cancer Cell Growth by Inducing G2/M Cell Cycle Arrest and Apoptosis
Stereoisomers of Astaxanthin Inhibit Human Colon Cancer Cell Growth by Inducing G2/M Cell Cycle Arrest and Apoptosis
复制标题
虾青素立体异构体通过诱导 G2/M 细胞周期停滞和凋亡来抑制人结肠癌细胞生长
DOI：
10.1021/acs.jafc.6b03636
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发表时间：
2016-10-19
影响因子：
6.1
通讯作者：
Xiao, Hang
中科院分区：
文献类型：
--
作者：
Liu, Xiaojuan;Song, Mingyue;Xiao, Hang
虾青素(AST)是一种叶黄素类胡萝卜素，具有潜在的抗癌保护作用。天冬氨酸转氨酶(AST)的不同立体异构体存在于各种食物来源中。由于对AST生物活性的了解有限，本研究探讨了ASTS对人结肠癌细胞株HCT116和HT29的抑制作用。所研究的AST包括雨生红球藻的3S，3‘S(S)，法夫酵母的3R，3’R(R)，以及合成的天冬氨酸转氨酶的统计混合物(S：MESO：R=1：2：1)(M)。细胞存活率测定显示，AST均以时间依赖(24-72 h)和剂量依赖(4-16µM)的方式抑制结肠癌细胞生长，其IC50值差异无统计学意义(p>；0.05)。流式细胞仪分析表明，ASTS诱导癌细胞发生G2/M期停滞和细胞凋亡。ASTS引起的细胞周期停滞与p21(Cip1)/(Waf1)、p27和P53表达水平升高以及CDK4和CDK6水平下降有关。同时，通过激活癌细胞中的caspase-3和PARP来证实ASTS诱导的细胞凋亡。结果表明，端环结构中C3和C3‘位的羟基可能不是影响AST抗癌活性的主要因素。本研究揭示了天冬氨酸对人结肠癌细胞的抑制作用，为将天冬氨酸作为结肠癌的化学预防药物提供了依据。
Astaxanthin (AST) is a xanthophyll carotenoid with potential protective effects against carcinogenesis. Different stereoisomers of AST (ASTs) exist in a variety of food sources. Due to limited information on the bioactivities of ASTs, the present study investigated the inhibitory effects of ASTs on HCT116 and HT29 human colon cancer cells. ASTs investigated herein included 3S,3'S (S) from Haematococcus pluvialis, 3R,3'R (R) from Phaffia rhodozyma, and a statistical mixture (S: meso: R = 1:2:1) (M) from synthetic AST. Cell viability assay showed that ASTs all inhibited colon cancer cell growth in a time dependent (24-72 h) and dose-dependent (4-16 mu M) manner, and there was no significant difference among the IC50 values of ASTs (p > 0.05). Flow cytometry analysis indicated that ASTs induced G2/M cell cycle arrest and cellular apoptosis in cancer cells. The cell cycle arrest caused by ASTs was associated with increases in the expression levels of p21(Cip1)/(Waf1), p27, and p53, as well as decreases in the levels of CDK4 and CDK6. Meanwhile, the apoptosis induced by ASTs was confirmed by activation of caspase-3 and PARP in the cancer cells. The results indicated that hydroxyl (OH) at C3 and C3' of terminal ring structure might not be the major factor that affects the anticancer activity of AST. This study revealed important information on the inhibitory effects of ASTs on human colon cancer cells, which provided a basis for using ASTs as chemopreventiiie agents for colon cancer.