纳米合成的 H2L 及其 Cu(II) 配合物诱导人肝癌细胞凋亡。
Induction of Apoptosis by Nano-Synthesized Complexes of H2L and its Cu(II) Complex in Human Hepatocellular Carcinoma Cells.
机构信息
Biochemistry Division, Chemistry Department, Faculty of Science, Tanta University, Tanta 31527, Egypt.
Chemistry Department, Faculty of Science, Tanta University, Tanta 31527, Egypt.
出版信息
Anticancer Agents Med Chem. 2021;21(9):1151-1159. doi: 10.2174/1871520620666200204103756.
BACKGROUND
Chemotherapy is currently the most utilized treatment for cancer. Therapeutic potential of metal complexes in cancer therapy has attracted a lot of interest. The mechanisms of action of most organometallic complexes are poorly understood.
OBJECTIVE
This study was designed to explore the mechanisms governing the anti-proliferative effect of the free ligand N1,N6-bis((2-hydroxynaphthalin-1-yl)methinyl)) adipohydrazone (H2L) and its complexes of Mn(II), Co(II), Ni(II) and Cu(II).
METHODS
Cells were exposed to H2L or its metal complexes where cell viability determined by MTT assay. Cell cycle was analysed by flow cytometry. In addition, qRT-PCR was used to monitor the expression of Bax and Bcl-2. Moreover, molecular docking was carried out to find the potentiality of Cu(II) complex as an inhibitor of Adenosine Deaminase (ADA). ADA, Superoxide Dismutase (SOD) and reduced Glutathione (GSH) levels were measured in the most affected cancer cell line.
RESULTS
The obtained results demonstrated that H2L and its Cu(II) complex exhibited a strong cytotoxic activity compared to other complexes against HepG2 cells (IC=4.14±0.036μM/ml and 3.2±0.02μM/ml), respectively. Both H2L and its Cu(II) complex induced G2/M phase cell cycle arrest in HepG2 cells. Additionally, they induced apoptosis in HepG2 cells via upregulation of Bax and downregulation of Bcl-2. Interestingly, the activity of ADA was decreased by 2.8 fold in HepG2 cells treated with Cu(II) complex compared to untreated cells. An increase of SOD activity and GSH level in HepG2 cells compared to control was observed.
CONCLUSION
The results concluded that Cu(II) complex of H2L induced apoptosis in HepG2 cells. Further studies are needed to confirm its anti-cancer effect in vivo.
背景
化疗是目前治疗癌症最常用的方法。金属配合物在癌症治疗中的治疗潜力引起了广泛关注。大多数有机金属配合物的作用机制还了解甚少。
目的
本研究旨在探讨游离配体 N1，N6-双((2-羟基萘-1-基)亚甲基)己二酰腙(H2L)及其 Mn(II)、Co(II)、Ni(II)和 Cu(II)配合物的抗增殖作用的调控机制。
方法
将细胞暴露于 H2L 或其金属配合物中，通过 MTT 测定法测定细胞活力。用流式细胞术分析细胞周期。此外，还使用 qRT-PCR 监测 Bax 和 Bcl-2 的表达。此外，还进行了分子对接，以寻找 Cu(II)配合物作为腺苷脱氨酶(ADA)抑制剂的潜力。在受影响最严重的癌细胞系中测量 ADA、超氧化物歧化酶(SOD)和还原型谷胱甘肽(GSH)水平。
结果
结果表明，与其他配合物相比，H2L 和其 Cu(II)配合物对 HepG2 细胞表现出更强的细胞毒性活性(IC=4.14±0.036μM/ml 和 3.2±0.02μM/ml)。H2L 和其 Cu(II)配合物均诱导 HepG2 细胞 G2/M 期细胞周期停滞。此外，它们通过上调 Bax 和下调 Bcl-2 诱导 HepG2 细胞凋亡。有趣的是，与未处理的细胞相比，用 Cu(II)配合物处理的 HepG2 细胞中 ADA 的活性降低了 2.8 倍。与对照相比，HepG2 细胞中的 SOD 活性和 GSH 水平增加。
结论
结果表明，H2L 的 Cu(II)配合物诱导 HepG2 细胞凋亡。需要进一步的研究来确认其在体内的抗癌作用。
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