Induction of DNA Damage and Apoptosis Mediate Cytotoxic by Oxaliplatin In Human Breast Cancer MCF-7 Cell Lines in Vitro

K. Habas
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Abstract

Cancer is an extremely disease leading cause of human death worldwide, and breast cancer is the most common type of malignancy in women. It is a heterogenous and hormone-dependent disease. Oxaliplatin is a novel platinum derivative and is a potent chemotherapeutic agent. Therefore, oxaliplatin is an apoptotic effectual compound for treating cancer with cytotoxic side effects. To explore the underlying mechanism of action of oxaliplatin, we examined the induction of apoptosis on human breast cancer MCF-7 cell lines by the drug and introduced its possible mechanism of action. The oxidative-induced DNA damage was evaluated by 8-hydroxy-2-deoxyguanosine (8-OHdG) reduction. The cellular pathways involved in the apoptosis of P53 and BCL2 were also assessed by qPCR and Western blotting assays. The results showed that oxaliplatin exposure causes increased oxidative stress levels and activation of P53, and repression of BCL2 was also involved in these mechanistic pathways.Graphical abstract on the apoptotic mechanism of oxaliplatin via P53 activation and repression of BCL2 in MCF-7 cells.
奥沙利铂在体外诱导人乳腺癌MCF-7细胞系DNA损伤和凋亡介导的细胞毒性
癌症是世界范围内导致人类死亡的主要疾病,乳腺癌是女性中最常见的恶性肿瘤。这是一种异质性和激素依赖性疾病。奥沙利铂是一种新型的铂衍生物,是一种有效的化疗药物。因此,奥沙利铂是治疗具有细胞毒性副作用的肿瘤细胞凋亡有效化合物。为了探索奥沙利铂的作用机制,我们研究了奥沙利铂对人乳腺癌MCF-7细胞株的凋亡诱导作用,并介绍了其可能的作用机制。通过8-羟基-2-脱氧鸟苷(8-OHdG)还原来评估氧化诱导的DNA损伤。通过qPCR和Western blotting检测参与P53和BCL2凋亡的细胞通路。结果表明,奥沙利铂暴露导致氧化应激水平升高和P53激活,而BCL2的抑制也参与了这些机制途径。图解摘要:奥沙利铂通过激活P53和抑制MCF-7细胞中BCL2的凋亡机制。
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