Protective role of cytoplasmic p21Cip1/Waf1 in apoptosis of CDK4/6 inhibitor-induced senescence in breast cancer cells.

ABSTRACT: Inhibition of CDK4/6 slows the cell cycle and induces senescence in breast cancer cells. However, senescent cancer cells promote invasion and metastasis. Several drugs reportedly target senescent cells, including ABT-263 (navitoclax). We examined the effects of the CDK4/6 inhibitor abemaciclib and ABT-263 on two human breast cancer cell lines. The abemaciclib and ABT-263 combination additively decreased the viability of MDA-MB-231 cells, but not MCF-7 cells. Also, the combination therapy-induced caspase-dependent apoptosis in MDA-MB-231 cells. Combination therapy with abemaciclib and ABT-737, an ABT-263 analog, significantly suppressed the in vivo growth of MDA-MB-231 with transient body-weight loss. Given that p16^Ink4a and p21^Cip1/Waf1 are key factors in senescence a

SUBMITTER: Kartika ID 

PROVIDER: S-EPMC8683524 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature