Mirshamsi Mohammad Reza, Omranipour Ramesh, Vazirizadeh Amir, Fakhri Amir, Zangeneh Fatemeh, Mohebbi Gholam Hussain, Seyedian Ramin, Pourahmad Jalal
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Email:
Asian Pac J Cancer Prev. 2017 Jan 1;18(1):277-286. doi: 10.22034/APJCP.2017.18.1.277.
Objective: This study was conducted to investigate whether fractions of jellyfish Cassiope andromeda venom, could selectively induce toxicity on mitochondria isolated from cancer tissue of patients with breast adenocarcinomas. Methods: Firstly, we extracted two fractions, (f1 and f2) from crude jellyfish venom by gel filtration on Sephadex G-200.Then different dilutions of these extracted fractions were applied to mitochondria isolated from human breast tumoral- and extra-tumoral tissues. Parameters of mitochondrial toxicity including generation of reactive oxygen species (ROS), mitochondrial membrane potential (MMP) collapse, swelling, cytochrome c release, activation of caspase3 and apoptosis were then assayed. Result: Our results demonstrate that fraction 2 of Cassiopea andromeda crude venom significantly (P<0.05) decreased mitochondrial succinate dehydrogenase activity, increased mitochondrial ROS production, induced mitochondrial swelling, MMP collapse and cytochrome c release, activated caspase3 and induced apoptosis only in tumoral mitochondria, and not in mitochondria obtained from extra-tumoral tissue (P<0.05). Conclusion: In conclusion this study suggested that fraction 2 of Cassiopea andromeda crude venom selectively induces ROS mediated cytotoxicity by directly targeting mitochondria isolated from human breast tumor tissue.
本研究旨在调查仙女水母毒液的不同组分是否能对从乳腺腺癌患者癌组织中分离出的线粒体选择性地诱导毒性作用。方法:首先,我们通过在葡聚糖凝胶G - 200上进行凝胶过滤,从粗制水母毒液中提取了两个组分(f1和f2)。然后将这些提取组分的不同稀释液应用于从人乳腺肿瘤组织和肿瘤外组织中分离出的线粒体。随后检测线粒体毒性参数,包括活性氧(ROS)生成、线粒体膜电位(MMP)崩溃、肿胀、细胞色素c释放、半胱天冬酶3激活和细胞凋亡。结果:我们的结果表明,仙女水母粗毒液的组分2显著(P<0.05)降低线粒体琥珀酸脱氢酶活性,增加线粒体ROS生成,诱导线粒体肿胀、MMP崩溃和细胞色素c释放,激活半胱天冬酶3并仅在肿瘤线粒体中诱导细胞凋亡,而在从肿瘤外组织获得的线粒体中未出现(P<0.05)。结论:总之,本研究表明仙女水母粗毒液的组分2通过直接靶向从人乳腺肿瘤组织中分离出的线粒体,选择性地诱导线粒体活性氧介导的细胞毒性。