State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Physiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
Pharmaceutical Animal Experimental Center, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
Life Sci. 2021 May 1;272:119196. doi: 10.1016/j.lfs.2021.119196. Epub 2021 Feb 19.
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.
衰老的癌细胞有助于肿瘤产生抗药性。化疗后清除衰老细胞可以预防或延缓癌症复发。我们的研究表明，GL-V9（5-羟基-8-甲氧基-2-苯基-7-(4-(吡咯烷-1-基)丁氧基)-4-H-色烯-4-酮），一种有潜力的抗癌药物，能够清除衰老的 MEFs（小鼠胚胎成纤维细胞）和药物诱导的乳腺癌衰老细胞。GL-V9 诱导衰老的 MDA-MB-231 细胞发生细胞凋亡。其作用机制为使溶酶体碱化，增加线粒体和 ROS（活性氧）的丰度。在 MMTV-PyMT 小鼠的表阿霉素处理的乳腺肿瘤中也观察到 GL-V9 的衰老细胞清除作用。因此，我们的数据表明，GL-V9 是一种很有前途的衰老细胞清除药物，可用于改善癌症化疗的效果。
