Guneidy R A, Zaki E R, Karim G S A Abdel, Saleh N S, Shokeer A
Department of Molecular Biology, Biotechnology Research Institute, National Research Centre, Cairo, Egypt.
J Genet Eng Biotechnol. 2023 Nov 21;21(1):131. doi: 10.1186/s43141-023-00564-z.
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.
After 48 h of incubation at IC 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.
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.
乳腺癌是全球女性面临的最重大威胁。大多数化疗药物通过诱导氧化应激和产生活性氧（ROS）来导致癌细胞死亡和凋亡。癌细胞的代谢活性率高于正常细胞，因此会产生更多的ROS。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抗氧化防御机制。酚类化合物的抗癌作用已得到充分证实。将酚类化合物作为药物与化疗联合使用可能会改善健康状况、提高治疗效果并减少剂量和损伤。本研究的目的是单独使用罗望子提取物以及将其与抗癌药物他莫昔芬（TAM）联合用于治疗乳腺癌细胞系（MCF-7），以提高治疗效果。
在罗望子提取物（47.3 μg/mL）、他莫昔芬（0.8 μg/mL）及其联合处理的IC浓度下孵育48小时后，研究了对MCF-7细胞系的生化和遗传毒性作用。在MCF7细胞系中，罗望子提取物增加了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的活性。氧化状态指标也是如此，过氧化氢酶和乳酸脱氢酶活性较高的水平与丙二醛水平较高相关。罗望子对DNA损伤参数几乎没有影响。所有这些变化都可能导致癌细胞遗传毒性和凋亡途径的改变，解释了DNA瞬间恢复到正常水平并提高了存活率。
罗望子提取物处理的细胞毒性和遗传毒性作用可归因于谷胱甘肽循环和抗氧化酶的动态相互作用以对抗氧化应激，这可被视为一种积极的治疗效果。另一方面，与罗望子联合处理时他莫昔芬疗效的负面反应逆转了他莫昔芬的遗传毒性并提高了存活率。
