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MMTV-PyMT小鼠
LIFE SCIENCES · 2021 · IF 5.037

Identification of GL-V9 as a novel senolytic agent against senescent breast cancer cells

Dawei Yang,Xiaoyu Tian,Yuchen Ye,Yin Liang,Jie Zhao,Tao Wu,Na Lu

Senescent cancer cells contribute to tumor refractoriness. The removal of senescent cells after chemotherapy prevents or delays cancer relapse. Our study showed that GL-V9 (5-hydroxy-8-methoxy-2-phenyl-7-(4-(pyrrolidin-1-yl) butoxy)-4-H-chromen-4-one), a potential anticancer drug, eliminated senescent MEFs (Mouse embryonic fibroblasts) and drug-induced senescent breast cancer cells. GL-V9 induced apoptosis in senescent MDA-MB-231 cells. Mechanistically, it alkalized lysosomes and increased the abundance of mitochondria as well as ROS (Reactive oxygen species). The senolytic effect of GL-V9 was also observed in epirubicin-treated mammary tumors in MMTV-PyMT mice. Our data thus indicated that GL-V9 is a promising senolytic drug which could be used to improve the outcome of cancer chemotherapy.

研究领域: 肿瘤学 · 药理学 · 细胞生物学
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