Kennedy R Kamaraj, Veena V, Naik P Ravindra, Lakshmi Pragna, Krishna R, Sudharani S, Sakthivel N
Department of Biotechnology, School of Life Sciences, Pondicherry University, Kalapet, Puducherry, 605014, India.
Apoptosis. 2015 Jun;20(6):858-68. doi: 10.1007/s10495-015-1118-0.
Phenazine-1-carboxamide (PCN), a naturally occurring simple phenazine derivative isolated from Pseudomonas sp. strain PUP6, exhibited selective cytotoxic activity against lung (A549) and breast (MDA-MB-231) cancer cell lines in differential and dose-dependent manner compared to normal peripheral blood mononuclear cells. PCN-treated cancer cells showed the induction of apoptosis as evidenced by the release of low level of LDH, morphological characteristics, production of reactive oxygen species, loss of mitochondrial membrane potential (ΔΨm) and induction of caspase-3. At molecular level, PCN instigates apoptosis by mitochondrial intrinsic apoptotic pathway via the overexpression of p53, Bax, cytochrome C release and activation of caspase-3 with the inhibition of oncogenic anti-apoptotic proteins such as PARP and Bcl-2 family proteins (Bcl-2, Bcl-w and Bcl-xL). The in silico docking studies of PCN targeted against the anti-apoptotic members of Bcl-2 family proteins revealed the interaction of PCN with the BH3 domain, which might lead to the induction of apoptosis due to the inhibition of antiapoptotic proteins. Due to its innate inhibition potential of antiapoptotic Bcl-2 family proteins, PCN may be used as potent anticancer agent against both lung and breast cancer.
吩嗪-1-甲酰胺（PCN）是一种从假单胞菌属菌株PUP6中分离出的天然存在的简单吩嗪衍生物，与正常外周血单核细胞相比，它对肺癌（A549）和乳腺癌（MDA-MB-231）细胞系表现出选择性细胞毒性活性，且具有差异和剂量依赖性。PCN处理的癌细胞显示出凋亡诱导，这通过低水平乳酸脱氢酶的释放、形态学特征、活性氧的产生、线粒体膜电位（ΔΨm）的丧失以及caspase-3的诱导得以证明。在分子水平上，PCN通过线粒体内在凋亡途径诱导凋亡，其机制包括p53、Bax的过表达、细胞色素C的释放、caspase-3的激活以及对致癌抗凋亡蛋白如PARP和Bcl-2家族蛋白（Bcl-2、Bcl-w和Bcl-xL）的抑制。PCN针对Bcl-2家族蛋白抗凋亡成员的计算机对接研究表明，PCN与BH3结构域相互作用，这可能由于抗凋亡蛋白的抑制而导致凋亡诱导。由于其对抗凋亡Bcl-2家族蛋白的固有抑制潜力，PCN可作为针对肺癌和乳腺癌的有效抗癌剂。
