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Senolytics (DQ) Mitigates Radiation Ulcers by Removing Senescent Cells
Front Oncol. 2020 Feb 14;9:1576. doi: 10.3389/fonc.2019.01576.
Huilan Wang 1 2, Ziwen Wang 2, Yu Huang 3, Yue Zhou 4, Xiaowu Sheng 4, Qingzhi Jiang 1 2, Yawei Wang 2, Peng Luo 2, Min Luo 3, Chunmeng Shi 1 2
Abstract:
Radiation ulcers are a prevalent toxic side effect in patients receiving radiation therapy...Here we demonstrate increased expression of p16 (a senescence biomarker) in human radiation ulcers after radiotherapy and radiation-induced persistent cell senescence in animal ulcer models. Furthermore, senescent cells secreted the senescence-associated secretory phenotype (SASP) and induced cell senescence in adjacent cells, which was alleviated by JAK inhibition. In addition, the clearance of senescent cells following treatment with a senolytics cocktail, Dasatinib plus Quercetin (DQ), mitigated radiation ulcers. Finally, DQ induced tumor cell apoptosis and enhanced radiosensitivity in representative CAL-27 and MCF-7 cell lines. Our results demonstrate that cell senescence is involved in the development of radiation ulcers and that elimination of senescent cells might be a viable strategy for patients with this condition.
PMID: 32117790
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034035/
Tags: dasatinib, p16, quercetin, senolytics