Faculty of Science, Department of Biology and Ecology, University of Kragujevac, Kragujevac, Serbia.
Faculty of Science, Department of Chemistry, University of Kragujevac, Kragujevac, Serbia.
Drug Dev Res. 2022 May;83(3):688-698. doi: 10.1002/ddr.21900. Epub 2021 Nov 26.
Platinum(IV) complexes offer the potential to overcome cisplatin resistance of cancer cells, with possible improved selectivity. Resveratrol, a natural polyphenol with anticancer and antioxidant capacity, could limit the possible side effects of chemotherapeutics on healthy cells. This study investigates the effects of platinum(IV) complexes containing some esters of the ethylenediamine-N,N'-di-S,S-(2,2'-dibenzyl)acetate acid (H -S,S-eddba), and resveratrol on proliferation, migration, and redox balance of breast cancer (MDA-MB-231), choriocarcinoma (JEG-3), and human lung fibroblast (MRC-5) cell line. According to IC values, all complexes exhibited a significantly stronger antiproliferative effect on tested cell lines compared to cisplatin. Due to reduced adverse effects on MRC-5 cells, the complex containing ethyl-substituent (10 μM) was selected for further examination with resveratrol (25 μM) cotreatment. Resveratrol enhanced the survival of MRC-5 cells while diminished the viability of both used cancer cell lines when applied combined with selected complex. Furthermore, cotreatment of these two compounds decreased the migratory potential of tested cancer cell lines. The examined platinum(IV) complex was able to induce oxidative stress in all tested cell lines. Resveratrol proved to be efficient in protecting MRC-5 cells from complex-induced oxidative damage, while it significantly amplified antiproliferative, antimigratory, and prooxidative effects of platinum(IV) complex on both examined cancer cell lines. These findings may be valuable in elucidating the mechanism of action of platinum(IV) drugs, which should be further investigated.
铂(IV)配合物具有克服癌细胞顺铂耐药性的潜力,可能具有更高的选择性。白藜芦醇是一种具有抗癌和抗氧化能力的天然多酚,可以限制化疗药物对健康细胞的可能副作用。本研究调查了含有乙二胺-N,N'-二-S,S-(2,2'-二苄基)乙酸(H-S,S-eddba)酯的铂(IV)配合物和白藜芦醇对乳腺癌(MDA-MB-231)、绒毛膜癌(JEG-3)和人肺成纤维细胞(MRC-5)细胞系增殖、迁移和氧化还原平衡的影响。根据 IC 值,与顺铂相比,所有配合物对测试细胞系均表现出更强的抗增殖作用。由于对 MRC-5 细胞的不良反应减少,选择含有乙基取代基的配合物(10 μM)与白藜芦醇(25 μM)共同处理进行进一步研究。白藜芦醇增强了 MRC-5 细胞的存活率,同时降低了两种使用的癌细胞系的活力,当与选定的复合物一起应用时。此外,这两种化合物的联合处理降低了测试的癌细胞系的迁移潜力。所研究的铂(IV)配合物能够在所有测试的细胞系中诱导氧化应激。白藜芦醇被证明能够有效保护 MRC-5 细胞免受复合物诱导的氧化损伤,同时显著增强铂(IV)配合物对两种测试癌细胞系的增殖、迁移和促氧化作用。这些发现对于阐明铂(IV)药物的作用机制可能是有价值的,应该进一步研究。