School of Chemistry and Biosciences, University of Bradford, Bradford, UK.
School of Pharmacy and Medical Sciences, University of Bradford, Bradford, UK.
Arch Toxicol. 2021 Jan;95(1):337-343. doi: 10.1007/s00204-020-02938-5. Epub 2020 Oct 30.
Evading apoptosis and chemo-resistance are considered as very important factors which help tumour progression and metastasis. Hence, to overcome chemo-resistance, there is an urgent requirement for emergence of more effective treatment options. Myricetin, a naturally occurring flavonoid, is present in various plant-derived foods and shows antitumour potential in different cancers. In the present in vitro study, results from the comet assay demonstrated that myricetin bulk (10 µM) and nano (20 µM) forms exhibited a non-significant level of genotoxicity in lymphocytes from multiple myeloma patients when compared to those from healthy individuals. Western blot results showed a decrease in Bcl-2/Bax ratio and an increase in P53 protein levels in lymphocytes from myeloma patients, but not in lymphocytes from healthy individuals. A significant increase in intracellular reactive oxygen species level was also observed, suggesting that regulation of apoptotic proteins triggered by myricetin exposure in lymphocytes from myeloma patients occurred through P53 and oxidative stress-dependent pathways. The potency of myricetin against lymphocytes from myeloma patients marks it a potential candidate to be considered as an alternative to overcome chemo-resistance in cancer therapies.
逃避细胞凋亡和化疗耐药被认为是促进肿瘤进展和转移的非常重要的因素。因此，为了克服化疗耐药，迫切需要出现更有效的治疗选择。杨梅素是一种天然存在的类黄酮，存在于各种植物源性食品中，在不同类型的癌症中表现出抗肿瘤潜力。在本体外研究中，彗星试验结果表明，与健康个体相比，大量（10 μM）和纳米（20 μM）形式的杨梅素在多发性骨髓瘤患者的淋巴细胞中表现出非显著水平的遗传毒性。Western blot 结果显示，骨髓瘤患者的淋巴细胞中 Bcl-2/Bax 比值降低，P53 蛋白水平升高，但健康个体的淋巴细胞中则没有。还观察到细胞内活性氧水平显著增加，表明杨梅素暴露在骨髓瘤患者的淋巴细胞中引发的凋亡蛋白的调节是通过 P53 和氧化应激依赖途径发生的。杨梅素对骨髓瘤患者淋巴细胞的作用使其成为一种有潜力的候选药物，可以考虑作为克服癌症治疗中化疗耐药的替代药物。
