Hajrezaie Maryam, Paydar Mohammadjavad, Moghadamtousi Soheil Zorofchian, Hassandarvish Pouya, Gwaram Nura Suleiman, Zahedifard Maryam, Rouhollahi Elham, Karimian Hamed, Looi Chung Yeng, Ali Hapipah Mohd, Abdul Majid Nazia, Abdulla Mahmood Ameen
Department of Biomedical Science, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia ; Faculty of Science, Institute of Biological Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia.
ScientificWorldJournal. 2014 Mar 5;2014:540463. doi: 10.1155/2014/540463. eCollection 2014.
Metal-based drugs with extensive clinical applications hold great promise for the development of cancer chemotherapeutic agents. In the last few decades, Schiff bases and their complexes have become well known for their extensive biological potential. In the present study, we examined the antiproliferative effect of a copper (II) complex on HT-29 colon cancer cells. The Cu(BrHAP)2 Schiff base compound demonstrated a potent antiproliferative effect in HT-29 cells, with an IC50 value of 2.87 μg/ml after 72 h of treatment. HT-29 cells treated with Cu (II) complexes underwent apoptosis death, as exhibited by a progressive elevation in the proportion of the G1 cell population. At a concentration of 6.25 μg/ml, the Cu(BrHAP)2 compound caused significant elevation in ROS production following perturbation of mitochondrial membrane potential and cytochrome c release, as assessed by the measurement of fluorescence intensity in stained cells. Furthermore, the activation of caspases 3/7 and 9 was part of the Cu (II) complex-induced apoptosis, which confirmed the involvement of mitochondrial-mediated apoptosis. Meanwhile, there was no significant activation of caspase-8. Taken together, these results imply that the Cu(BrHAP)2 compound is a potential candidate for further in vivo and clinical colon cancer studies to develop novel chemotherapeutic agents derived from metal-based agents.
具有广泛临床应用的金属基药物在癌症化疗药物的开发中具有巨大潜力。在过去几十年中，席夫碱及其配合物因其广泛的生物活性而闻名。在本研究中，我们检测了一种铜（II）配合物对HT-29结肠癌细胞的抗增殖作用。Cu(BrHAP)2席夫碱化合物在HT-29细胞中表现出强大的抗增殖作用，处理72小时后的IC50值为2.87μg/ml。用铜（II）配合物处理的HT-29细胞发生凋亡死亡，表现为G1期细胞比例逐渐升高。在浓度为6.25μg/ml时，通过测量染色细胞中的荧光强度评估，Cu(BrHAP)2化合物在干扰线粒体膜电位和细胞色素c释放后导致活性氧生成显著增加。此外，半胱天冬酶3/7和9的激活是铜（II）配合物诱导凋亡的一部分，这证实了线粒体介导的凋亡参与其中。同时，半胱天冬酶-8没有明显激活。综上所述，这些结果表明Cu(BrHAP)2化合物是进一步进行体内和临床结肠癌研究以开发源自金属基药物的新型化疗药物的潜在候选物。
