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Doxorubicin-induced senescence in normal fibroblasts promotes in vitro tumour cell growth and invasiveness: The role of Quercetin in modulating these processes
Mechanisms of Ageing and Development ( IF 5.3 ) Pub Date : 2022-06-18 , DOI: 10.1016/j.mad.2022.111689
Elisa Bientinesi 1 , Matteo Lulli 1 , Matteo Becatti 1 , Sara Ristori 1 , Francesca Margheri 1 , Daniela Monti 1
Affiliation  

Ageing is a complex biological phenomenon representing the major risk factor for developing age-related diseases, such as cardiovascular pathologies, neurodegenerative diseases, and cancer. Geroscience, the new vision of gerontology, identifies cellular senescence as an interconnected biological process that characterises ageing and age-related diseases. Therefore, many strategies have been employed in the last years to reduce the harmful effects of senescence, and among these, the most intriguing ones use nutraceutical compounds. Here we show that a pre-treatment with Quercetin, a bioactive flavonoid present in many fruits and vegetables, increasing cellular antioxidant defence, can alleviate Doxorubicin (Doxo)-induced cellular senescence in human normal WI-38 fibroblasts.

Furthermore, our work demonstrates that Quercetin pre-treatment, reducing the number of senescent cells and the production of the senescence-associated secretory phenotype (SASP) factors, can decrease the pro-tumour effects of conditioned medium from Doxo-induced senescent fibroblasts on osteosarcoma cells. Overall, our findings are consistent with the hypothesis that targeting senescent cells can be an emerging strategy for cancer treatment, especially in elderly patients, in which senescent cells are already abundant in several tissues and organs.



中文翻译:

阿霉素诱导的正常成纤维细胞衰老促进体外肿瘤细胞生长和侵袭性:槲皮素在调节这些过程中的作用

衰老是一种复杂的生物学现象,代表了发展与年龄相关的疾病的主要风险因素,例如心血管疾病、神经退行性疾病和癌症。Geroscience 是老年学的新视野,将细胞衰老确定为一个相互关联的生物学过程,该过程以衰老和与年龄相关的疾病为特征。因此,过去几年已经采用了许多策略来减少衰老的有害影响,其中最有趣的策略是使用营养保健化合物。在这里,我们展示了用槲皮素(一种存在于许多水果和蔬菜中的生物活性类黄酮)进行预处理,增加细胞的抗氧化防御能力,可以缓解多柔比星 (Doxo) 诱导的人类正常 WI-38 成纤维细胞中的细胞衰老。

此外,我们的工作表明,槲皮素预处理,减少衰老细胞的数量和衰老相关分泌表型 (SASP) 因子的产生,可以降低来自 Doxo 诱导的衰老成纤维细胞的条件培养基对骨肉瘤的促肿瘤作用细胞。总体而言,我们的研究结果与以下假设一致,即靶向衰老细胞可能是一种新兴的癌症治疗策略,特别是在老年患者中,其中衰老细胞已经在多个组织和器官中丰富。

更新日期:2022-06-18
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