Resveratrol Modulates the Redox-status and Cytotoxicity of Anticancer Drugs by Sensitizing Leukemic Lymphocytes and Protecting Normal Lymphocytes
Resveratrol Modulates the Redox-status and Cytotoxicity of Anticancer Drugs by Sensitizing Leukemic Lymphocytes and Protecting Normal Lymphocytes
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DOI：
10.21873/anticanres.13523
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发表时间：
2019-07-01
影响因子：
2
通讯作者：
Bakalova, Rumiana
中科院分区：
文献类型：
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作者：
Ivanova, Donika;Zhelev, Zhivko;Bakalova, Rumiana
背景/目的：该研究针对白藜芦醇对白血病和正常淋巴细胞的氧化还原状态和活力的影响，以及其使白血病淋巴细胞对抗癌药物敏感的能力。材料与方法：通过台盼蓝染色、细胞凋亡（通过膜联蛋白V试验）和氧化应激（通过活性氧（ROS）和蛋白质羰基产物的细胞内水平）分析细胞毒性。结果：白藜芦醇与大多数抗癌药物联合孵育比白藜芦醇或单独药物的毒性更高。在白藜芦醇存在的情况下，用barasertib和依维莫司处理白血病淋巴细胞的情况下，协同细胞毒性伴随着强烈的细胞凋亡诱导，氢过氧化物水平增加和蛋白质-羰基产物的微小变化。这些参数在正常淋巴细胞中无变化。结论：白藜芦醇是一种有效的抗肿瘤药物。用于抗癌治疗的有前景的补充化合物，其可允许降低barasertib和依维莫司的治疗剂量，使其副作用最小化。
Background/Aim: The study is directed to the effect of resveratrol on the redox-status and viability of leukemic and normal lymphocytes, as well as its ability to sensitize leukemic lymphocytes to anticancer drugs. Materials and Methods: Cytotoxicity was analyzed by trypan blue staining, apoptosis - by Annexin V test, and oxidative stress - by the intracellular levels of reactive oxygen species (ROS) and protein-carbonyl products. Results: Incubation of resveratrol in combination with the majority of anticancer drugs resulted in higher toxicity than resveratrol or drug alone. In the case of leukemic lymphocytes treated with barasertib and everolimus in the presence of resveratrol, synergistic cytotoxicity was accompanied by strong induction of apoptosis, increased levels of hydroperoxides and insignificant changes in protein-carbonyl products. None of these parameters changed in normal lymphocytes. Conclusion: Resveratrol is. promising supplementary compound for anticancer therapy, that may allow reduction of the therapeutic doses of barasertib and everolimus, minimizing their side-effects.