Hassan Firas, El-Hiti Gamal A, Abd-Allateef Mays, Yousif Emad
Department of Chemistry, College of Science, Al-Nahrain University, Baghdad, Iraq. E-mail.
Saudi Med J. 2017 Apr;38(4):359-365. doi: 10.15537/smj.2017.4.17061.
To investigate the cytotoxic effect of anastrozole on breast (MCF7), liver hepatocellular (HepG2), and prostate (PC3) cancer cells. Methods: This is a prospective study. Anastrozole's mechanism of apoptosis in living cells was also determined by high content screening (HCS) assay. Methylthiazol tetrazolium (MTT) assay was carried out at the Centre of Biotechnology Research's, Al-Nahrain University, Baghdad, Iraq between July 2015 and October 2015. The HCS assay was performed at the Centre for Natural Product Research and Drug Discovery, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia between November 2015 and February 2016. Results: The most significant cytotoxic effect of anastrozole towards 3 cancer cell lines was obtained when its concentration was 400 µg/mL. The MCF7 cells were more sensitive to anastrozole compared with the HepG2 and PC-3 cells. There was a significant increase in membrane permeability, cytochrome c and nuclear intensity when anastrozole (200 µg/mL) was used compared with doxorubicin (20 µg/mL) as a standard. Also, there was a significant decrease in cell viability and mitochondrial membrane permeability when anastrozole (200 µg/mL) was used compared with positive control. Conclusion: Anastrozole showed cytotoxic effects against the MCF7, HepG2, and PC3 cell lines as determined in-vitro by the MTT assay. The HCS technique also showed toxic effect towards MCF7. It is evident that anastrozole inhibits the aromatase enzyme preventing the aromatization mechanism; however, it has a toxic effect.
研究阿那曲唑对乳腺癌(MCF7)、肝癌(HepG2)和前列腺癌(PC3)细胞的细胞毒性作用。方法:这是一项前瞻性研究。还通过高内涵筛选(HCS)测定法确定了阿那曲唑在活细胞中的凋亡机制。2015年7月至2015年10月期间,在伊拉克巴格达的纳赫兰大学的生物技术研究中心进行了甲基噻唑四氮唑(MTT)测定。2015年11月至2016年2月期间,在马来西亚吉隆坡马来亚大学医学院药理学系的天然产物研究与药物发现中心进行了HCS测定。结果:当阿那曲唑浓度为400μg/mL时,其对3种癌细胞系的细胞毒性作用最为显著。与HepG2和PC-3细胞相比,MCF7细胞对阿那曲唑更敏感。与作为标准的多柔比星(20μg/mL)相比,使用阿那曲唑(200μg/mL)时膜通透性、细胞色素c和核强度显著增加。此外,与阳性对照相比,使用阿那曲唑(200μg/mL)时细胞活力和线粒体膜通透性显著降低。结论:MTT测定法体外测定结果表明,阿那曲唑对MCF7、HepG2和PC3细胞系具有细胞毒性作用。HCS技术也显示对MCF7有毒性作用。显然,阿那曲唑抑制芳香化酶,阻止芳香化机制;然而,它具有毒性作用。