Induction of apoptosis in A431 skin cancer cells by Cissus quadrangularis Linn stem extract by altering Bax-Bcl-2 ratio, release of cytochrome c from mitochondria and PARP cleavage
Induction of apoptosis in A431 skin cancer cells by Cissus quadrangularis Linn stem extract by altering Bax-Bcl-2 ratio, release of cytochrome c from mitochondria and PARP cleavage
复制标题
DOI：
10.1039/c2fo30167a
复制
发表时间：
2013-02-01
期刊：
影响因子：
6.1
通讯作者：
Patil, M. B.
中科院分区：
文献类型：
--
作者：
Bhujade, Arti;Gupta, G.;Patil, M. B.
皮肤通常通过遗传和环境因素如吸烟、暴露于外源性物质、热、激素变化和紫外线而受损。这些因素会导致皮肤病。四棱藤(CQ)自古以来就在民间医学中用于治疗皮肤病。考虑到该属植物所表现出的药用特性，决定研究CQ的抗癌活性。使用A431（皮肤表皮样癌，人）细胞系对从CQ获得的提取物及其酚类含量进行体外抗癌活性评价。以剂量依赖的方式用CQ的不同提取物处理A431细胞。在五种提取物中，丙酮提取物在A431细胞系中表现出显著的抗癌活性。己烷、氯仿、乙酸乙酯和甲醇浸提液也表现出细胞毒性，但程度相对低于丙酮浸提液。发现丙酮提取物的GI（50）值为8 μ g mL（-1），而丙酮提取物的纯化级分（称为AFCQ（CQ的活性丙酮级分））相对于A431细胞的GI（50）值为4.8 μ g mL（-1）。此外，通过评估AFCQ和DOX处理A431细胞后凋亡标志物的状态，将其效果与标准抗癌药物阿霉素（DOX）进行比较，研究AFCQ表现出的抗癌活性的机制。还评价了细胞凋亡的标志物-Bcl-2比率沿着细胞色素c从线粒体释放到细胞质。PARP裂解显示AFCQ诱导A431细胞凋亡，与DOX相比。
Skin is generally damaged through genetic and environmental factors such as smoking, exposure to xenobiotics, heat, hormonal changes, and ultraviolet light. These factors can cause skin diseases. Cissus quadrangularis Linn. (CQ) has been used in folk medicine for the treatment of skin diseases since ancient times. Taking in to consideration the medicinal properties exhibited by this genus, it was decided to investigate the anti-cancer activity of CQ. Extracts obtained from CQ and their phenolic contents were subjected to in vitro evaluation of anticancer activity by using A431 (skin epidermoid carcinoma, human) cell line. The A431 cells were treated with different extracts of CQ in a dose dependent manner. Out of five extracts, the acetone extract demonstrated significant anti-cancer activity in the A431 cell line. Hexane, chloroform, ethyl acetate and methanol extracts also exhibited cytotoxicity but to a comparatively lesser extent than the acetone extract. The GI(50) value of the acetone extract was found to be 8 mu g mL(-1), whereas GI(50) value of purified fraction of acetone extract, termed as AFCQ (active acetone fraction of CQ) with respect to A431 cells, was found to be 4.8 mu g mL(-1). Furthermore, the mechanism of anticancer activity exhibited by AFCQ was investigated by comparing its effect with the standard anticancer drug Doxorubicin (DOX) by evaluating the status of apoptotic markers after treatment of A431 cells with AFCQ and DOX. Bax-Bcl-2 ratio along with the release of cytochrome c from mitochondria to cytoplasm, which is a hallmark of apoptosis, was also evaluated. Cleavage of PARP revealed that AFCQ induces apoptosis in A431 cells with reference to DOX.