Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Ministry of Jihad-e-Agriculture, Research and Education and Extension Organization (AREEO) and The Iranian Fisheries Research Organization, 14155-6116 Tehran, Iran.
Mar Drugs. 2017 Oct 16;15(10):314. doi: 10.3390/md15100314.
Hepatocellular carcinoma (HCC), also named cancerous hepatoma, is the most common type of malignant neoplasia of the liver. In this research, we screened the Persian Gulf sea cucumber () methanolic sub-fractions for the possible existence of selective toxicity on liver mitochondria isolated from an animal model of HCC. Next, we purified the most active fraction. Thus the structure of the active molecule was identified. HCC was induced by diethylnitrosamine (DEN) and 2-acetylaminofluorene (2-AAF) protocol. Rat liver mitochondria for evaluation of the selective cytotoxic effects of sub-fractions of were isolated and then mitochondrial parameters were determined. Our results showed that C1 sub-fraction of methanolic extract of considerably increased reactive oxygen species (ROS) generation, collapse of mitochondrial membrane potential (MMP), swelling in mitochondria and cytochrome c release only on HCC liver mitochondria. Furthermore, the methanolic extract of was investigated furthermore and the active fraction was extracted. In this fraction, ()-2,3-diphenylacrylonitrile molecule, which is also known as α-cyanostilbene, was identified by mass analysis. This molecule increased ROS generation, collapse of MMP, swelling in mitochondria and finally cytochrome c release only on HCC liver mitochondria. The derivatives of ()-2,3-diphenylacrylonitrile in other natural products were also reported as an anti-cancer agent. These results suggest the eligibility of the ()-2,3-diphenylacrylonitrile as a complementary therapeutic agent for patients with HCC.
肝细胞癌(HCC),又称肝癌,是肝脏最常见的恶性肿瘤类型。在这项研究中,我们筛选了波斯湾海参的甲醇亚馏分,以研究其对 HCC 动物模型分离的肝线粒体是否存在选择性毒性。接下来,我们对最活跃的馏分进行了纯化。因此,确定了活性分子的结构。通过二乙基亚硝胺(DEN)和 2-乙酰氨基芴(2-AAF)方案诱导 HCC。评估 的亚馏分对大鼠肝线粒体的选择性细胞毒性作用,然后分离大鼠肝线粒体,并测定线粒体参数。我们的结果表明, 的甲醇提取物 C1 亚馏分仅在 HCC 肝线粒体上显著增加活性氧(ROS)生成、线粒体膜电位(MMP)崩溃、线粒体肿胀和细胞色素 c 释放。此外,还进一步研究了 的甲醇提取物,并提取了活性馏分。在该馏分中,通过质谱分析鉴定出()-2,3-二苯基丙烯腈分子,也称为α-氰基芪。该分子仅在 HCC 肝线粒体上增加 ROS 生成、MMP 崩溃、线粒体肿胀,最终导致细胞色素 c 释放。()-2,3-二苯基丙烯腈在其他天然产物中的衍生物也被报道为抗癌剂。这些结果表明,()-2,3-二苯基丙烯腈作为 HCC 患者的辅助治疗剂是合适的。