柽柳和他莫昔芬联用对乳腺癌细胞氧化还原平衡及遗传毒性的影响。

IF 3.6 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Journal, genetic engineering & biotechnology Pub Date : 2023-11-21 DOI:10.1186/s43141-023-00564-z
R A Guneidy, E R Zaki, G S A Abdel Karim, N S Saleh, A Shokeer
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引用次数: 0

摘要

背景:乳腺癌是全世界妇女面临的最大威胁。大多数化疗药物通过诱导氧化应激和产生活性氧(ROS)导致癌细胞死亡和凋亡。癌细胞比正常细胞具有更高的代谢活性,因此产生更多的活性氧。谷胱甘肽及其相关酶是保护细胞免受氧化和化疗影响的最重要的抗氧化防御机制。酚类化合物的抗癌作用得到了极大的证实。使用酚类化合物作为药物联合化疗可以改善健康,改善治疗结果,减少剂量和损害。本研究的目的是用柽柳提取物单独或联合抗癌药物他莫昔芬(TAM)治疗乳腺癌细胞株(MCF-7),以提高治疗效果。结果:以IC25浓度的籼米提取物(47.3 g/mL)、他莫昔芬(0.8 g/mL)及其共处理MCF-7细胞48 h后,观察其对MCF-7细胞的生化和遗传毒性影响。在MCF7细胞系中,籼稻提取物增加还原型谷胱甘肽水平以及谷胱甘肽转移酶、谷胱甘肽过氧化物酶和谷胱甘肽还原酶活性。氧化状态指标也是如此,过氧化氢酶和乳酸脱氢酶活性水平越高,丙二醛水平越高。籼稻对DNA损伤参数几乎没有影响。所有这些变异都能产生癌细胞遗传毒性和凋亡途径的改变,解释了DNA时刻恢复到正常水平和提高生存率的原因。结论:籼稻提取物的细胞毒性和遗传毒性作用可能与谷胱甘肽循环和抗氧化酶对抗氧化应激的动态相互作用有关,可认为是一种积极的治疗作用。另一方面,他莫昔芬与印度弓形虫共同治疗时,其疗效的负反应逆转了他莫昔芬的遗传毒性,提高了生存率。
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Adverse effect of Tamarindus indica and tamoxifen combination on redox balance and genotoxicity of breast cancer cell.

Background: Breast cancer is the most significant threat to women worldwide. Most chemotherapeutic drugs cause cancer cell death and apoptosis by inducing oxidative stress and producing reactive oxygen species (ROS). Cancer cells have a higher rate of metabolic activity than normal cells and thus produce more ROS. Glutathione and its related enzymes are the most significant antioxidant defense mechanisms that protect cells from oxidative and chemotherapeutic impacts. The anticancer actions of phenolic compounds were greatly confirmed. Using phenolic compounds as drugs in combination with chemotherapy may improve health, improve treatment outcomes, and reduce dose and damage. The goal of the study was to treat breast cancer cell lines (MCF-7) with Tamarindus indica extract individually and in combination with the anticancer drug tamoxifen (TAM) to improve therapeutic efficacy.

Results: After 48 h of incubation at IC25 concentrations of T. indica extract (47.3 g/mL), tamoxifen (0.8 g/mL), and their co-treatments, the biochemical and genotoxic effects on MCF-7 cell lines were investigated. In MCF7 cell lines, T. indica extract increased reduced glutathione levels as well as glutathione transferase, glutathione peroxidase, and glutathione reductase activities. The same was true for oxidative state indicators, where higher levels of catalase and lactate dehydrogenase activity were associated with higher levels of malondialdehyde. T. indica has almost no effect on the DNA damage parameters. All of these variations can produce alterations in cancer cell genotoxicity and apoptotic pathways, explaining the restoration of DNA moment to normal levels and enhanced survival.

Conclusion: Cytotoxic and genotoxic effect of treatment with T. indica extract could be attributed to the dynamic interaction of glutathione cycle and antioxidant enzymes to combat oxidative stress, which can be considered as a positive therapeutic effect. On the other hand, the negative response of tamoxifen efficacy when co-treated with T. indica reversed tamoxifen's genotoxicity and enhanced survival.

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