Bixin Triggers Apoptosis of Human Hep3B Hepatocellular Carcinoma Cells: An Insight to Molecular and IN SILICO Approach
Bixin Triggers Apoptosis of Human Hep3B Hepatocellular Carcinoma Cells: An Insight to Molecular and IN SILICO Approach
复制标题
DOI：
10.1080/01635581.2018.1490445
复制
发表时间：
2018-01-01
影响因子：
2.9
通讯作者：
Periyasamy, Latha
中科院分区：
文献类型：
--
作者：
Kumar, Yogesh;Phaniendra, Alugoju;Periyasamy, Latha
肝细胞癌是最常见的肝癌，对常规化疗耐药。近几十年来，由于副作用和对常规化疗的耐药性，草药和补充剂的使用有所增加。由于类胡萝卜素Bixa Orellana L.的大量抗癌特性，其种子俗称红木最近获得了科学上的关注。然而，比欣诱导细胞凋亡的分子机制仍不清楚。胃必信可显著减少Hep3B细胞数量，细胞形态和细胞核形态发生改变，Annexin V/PI染色证实细胞发生了凋亡事件。进一步的DCFDA和罗丹明123荧光分光光度研究显示，活性氧自由基(ROS)的产生增加和线粒体膜电位(MMP)的丧失。ROS的产生导致DNA损伤，细胞周期停滞，Bax和FasL蛋白表达上调，caspase-9、caspase-8和caspase-3蛋白裂解。与促凋亡分子Bax和表面Fas配体的对接研究显示出能量有利的结合作用。综上所述，这些结果表明，必信能够调节外在和内在的凋亡分子，这表明它有可能成为肝细胞癌的候选分子。
Hepatocellular carcinoma (HCC) is the most common liver cancer and is known to be resistant to conventional chemotherapy. The use of herbal medicine and supplements has increased over recent decades following side effects and resistant to conventional chemotherapy. The seeds of Bixa orellana L. commonly known as annatto have recently gained scientific attention due to presence of a carotenoid bixin for its substantial anticancer properties. However, molecular mechanisms underlying bixin-induced apoptosis are still unclear. Treatment of bixin significantly decreased the number of Hep3B cells and morphological study revealed the change in cellular and nuclear morphology that trigger the events of apoptosis confirmed by annexin V/PI staining. Further DCFDA and rhodamine 123 spectrofluorimetry study showed elevation in reactive oxygen species (ROS) production and loss of mitochondrial membrane potential (MMP), respectively. ROS production caused DNA damage and apoptosis was marked by cell cycle arrest, up-regulation of Bax and FasL protein as well as cleavage of caspase-9, caspase-8 and caspase-3 protein. Docking study with pro-apoptotic molecule Bax and surface Fas ligand exhibited energetically favourable binding interaction. Collectively, these results suggest that bixin capable of modulating the extrinsic and intrinsic molecules of apoptosis indicating its potential for development of promising candidate for hepatocellular carcinoma.