Rezaei Azadeh, Khanamani Falahati-Pour Soudeh, Mohammadizadeh Fatemeh, Hajizadeh Mohammad Reza, Mirzaei Mohammad Reza, Khoshdel Alireza, Fahmidehkar Mohammad Ali, Mahmoodi Mehdi
Department of Clinical Biochemistry, Faculty of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
Pistachio Safety Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran. Email:
Asian Pac J Cancer Prev. 2018 Oct 26;19(10):2877-2884. doi: 10.22034/APJCP.2018.19.10.2877.
Objectives: In the present study, we aimed to identify the anti-proliferative potential of [Cu(L)(2imi)] complex [L = 2-(((5-chloro-2-oxyphenyl)imino)methyl)phenolato) and 2imi = 2-methyl imidazole] against HepG2 cells as an in vitro model of human hepatocellular carcinoma and normal mouse fibroblast L929 cells. Methods: The cytotoxic and apoptotic effects of [Cu(L)(2imi)] complex on HepG2 cells and normal fibroblasts (L929) were examined by MTT assay and flow cytometry, respectively. Results: Cytotoxicity induced by [Cu(L)(2imi)] complex was time dependent. Also, there was a positive correlation between cytotoxicity and an increase in Cu complex concentration. For HepG2 cells, the cell viability percentage was 50% at 58 μg/mL after 24 h treatment, whereas in the same concentration and conditions, the viability percentage was surprisingly higher (about 100%) for L929 cells. Also, after 48 h treatment, the viability percentage of HepG2 cells at 55 μg/mL concentration was 50% in contrast with 89.3% for L929 cells in the same conditions. Flow cytometry findings suggest that [Cu(L)(2imi)] complex is capable of decreasing cancer cell viability through apoptosis and did not efficiently activate the necrosis process. Conclusions: Finally, we found that [Cu(L)(2imi)] complex possess the potential for development as an anti-cancer drug for human hepatocellular carcinoma.
在本研究中，我们旨在确定[Cu(L)(2imi)]配合物[L = 2-(((5-氯-2-氧代苯基)亚氨基)甲基)苯酚根离子，2imi = 2-甲基咪唑]对人肝癌细胞系HepG2细胞以及正常小鼠成纤维细胞L929细胞的抗增殖潜力，其中HepG2细胞作为人肝细胞癌的体外模型。方法：分别通过MTT法和流式细胞术检测[Cu(L)(2imi)]配合物对HepG2细胞和正常成纤维细胞（L929）的细胞毒性和凋亡作用。结果：[Cu(L)(2imi)]配合物诱导的细胞毒性具有时间依赖性。此外，细胞毒性与铜配合物浓度的增加呈正相关。对于HepG2细胞，处理24小时后，在58μg/mL浓度下细胞活力百分比为50%，而在相同浓度和条件下，L929细胞的活力百分比出奇地高（约100%）。同样，处理48小时后，55μg/mL浓度下HepG2细胞的活力百分比为50%，而在相同条件下L929细胞为89.3%。流式细胞术结果表明，[Cu(L)(2imi)]配合物能够通过凋亡降低癌细胞活力，并且没有有效激活坏死过程。结论：最后，我们发现[Cu(L)(2imi)]配合物具有开发成为治疗人肝细胞癌抗癌药物的潜力。
