Abstract:
The effect of a new pyridoxine derivative B6NO on doxorubicin cytotoxicity and Nrf2-dependent cellular processes in vitro was studied. Antioxidant B6NO enhances the cytotoxic effect of doxorubicin on tumor cells, which is associated with G2/M cell division arrest and an increase in activity of proapoptotic enzyme caspase-3. The antioxidant promotes intracellular accumulation and nuclear translocation of Nrf2 transcription factor in non-tumor and tumor cells. In non-tumor cells, B6NO increases the expression of antioxidant system proteins and reduces ROS generation in the presence of doxorubicin. In tumor cells, no activation of Nrf2-dependent processes occurs under the action of the antioxidant. Our findings demonstrate the prospect of further studies of pyridoxine derivatives as antioxidants to reduce adverse reactions during chemotherapy.
摘要:
研究了新的吡哆醇衍生物B6NO对阿霉素细胞毒性和Nrf2依赖性细胞过程的影响。抗氧化剂B6NO增强阿霉素对肿瘤细胞的细胞毒作用,这与G2/M细胞分裂停滞和促凋亡酶caspase-3的活性增加有关。抗氧化剂促进Nrf2转录因子在非肿瘤细胞和肿瘤细胞中的细胞内积累和核转位。在非肿瘤细胞中,在存在阿霉素的情况下,B6NO增加抗氧化系统蛋白的表达并减少ROS的产生。在肿瘤细胞中,在抗氧化剂的作用下不发生Nrf2依赖性过程的激活。我们的发现证明了进一步研究吡哆醇衍生物作为抗氧化剂以减少化疗期间的不良反应的前景。