Journal
LIFE SCIENCES
Volume 272, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2021.119196
Keywords
GL-V9; Senolytics; ROS; Autophagy; Breast cancer
Funding
- National Natural Science Foundation of China [81803558, 82073877, 81872899, 81903626]
- Social Development Project of Jiangsu Provincial Science and Technology Department [BE2018711]
- Natural Science Foundation of Jiangsu Province [BK20180576, BK20190563]
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The study demonstrated that GL-V9 can eliminate senescent cancer cells and induce apoptosis, potentially improving the outcome of cancer chemotherapy.
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.
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