Enhancement of antitumor effects of berberine chloride with a copper(II) complex against human triple negative breast cancer: In vitro studies

IF 2.5 Q2 CHEMISTRY, MULTIDISCIPLINARY

Results in Chemistry Pub Date : 2024-10-30 DOI:10.1016/j.rechem.2024.101882

Duaa R. Alajroush , Brittney F. Anderson , Janae A. Bruce , Christian I. Lartey , Dazonte A. Mathurin , Sean T. Washington , Tanaya S. Washington , Sidy Diawara , Sakariyau A. Waheed , Kaylin L. Thomas , Stephen J. Beebe , Alvin A. Holder

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Abstract

In this study, the copper(II) complex [Cu(chromoneTSC)Cl₂]•0.5H₂O•0.0625C₂H₅OH (where chromoneTSC = (E)-N-Ethyl-2-((4-oxo-4H-chromen-3-yl)methylene)-hydrazinecarbothioamide) was synthesized and characterized; then used to carry out in vitro studies in combination with berberine chloride (BBC). The ligand and complex were characterized by elemental analysis, FTIR and NMR (¹H and ¹³C) spectroscopy, and conductivity measurements. The cytotoxic effect was analyzed by using the CCK-8 viability assay in cancer MDA-MB-231 VIM RFP and non-cancer MCF-10A cell lines. The IC₅₀ values for the complex and BBC were 21.2 ± 1.6 and 48.3 ± 2.4 μM, respectively at 24 h incubation, while the IC₅₀ value of the combination treatment was 9.3 ± 1.5 in cancer cells. The co-treatment group significantly increased the number of cells in G2 phase, indicating the growth arrest of cancer cells. Moreover, the combination group showed induction of both intrinsic and extrinsic apoptotic pathways. There was also a study on the effect of the combination treatment on receptor-interacting serine/threonine-protein kinase 3 (RIPK3) and mixed lineage kinase domain-like pseudokinase (MLKL) as biomarkers of necroptosis. The results showed activation of necroptosis after treatment with the combination of the copper complex and BBC via the activation of RIPK3–MLKL pathway.

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用铜（II）复合物增强氯化小檗碱对人类三阴性乳腺癌的抗肿瘤作用：体外研究

本研究合成并表征了铜(II)配合物[Cu(chromoneTSC)Cl2]-0.5H2O-0.0625C2H5OH（其中 chromoneTSC = (E)-N-乙基-2-((4-氧代-4H-苯并吡喃-3-基)亚甲基)-肼硫代甲酰胺），并将其与氯化小檗碱（BBC）结合起来进行体外研究。通过元素分析、傅立叶变换红外光谱和核磁共振（1H 和 13C）光谱以及电导率测量对配体和复合物进行了表征。在癌症 MDA-MB-231 VIM RFP 细胞系和非癌症 MCF-10A 细胞系中使用 CCK-8 细胞活力测定法分析了细胞毒性效应。孵育 24 小时后，复合物和 BBC 的 IC50 值分别为 21.2 ± 1.6 和 48.3 ± 2.4 μM，而联合处理对癌细胞的 IC50 值为 9.3 ± 1.5。联合治疗组明显增加了处于 G2 期的细胞数量，表明癌细胞生长停止。此外，联合治疗组还显示出诱导内在和外在凋亡途径的作用。还有一项研究探讨了联合治疗对作为坏死生物标志物的受体丝氨酸/苏氨酸蛋白激酶3（RIPK3）和混合系激酶域样假激酶（MLKL）的影响。研究结果表明，铜复合物和BBC联合治疗后，坏死细胞会通过激活RIPK3-MLKL途径被激活。

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来源期刊

Results in Chemistry Chemistry-Chemistry (all)

CiteScore

2.70

自引率

8.70%

发文量

380

审稿时长

56 days