RRC ID 73991
Author Suemura M, Shibutani S, Iwata H.
Title The endocytosis inhibitor dynasore induces a DNA damage response pathway that can be manipulated for enhanced apoptosis.
Journal Biochem Biophys Res Commun
Abstract Endocytosis has been shown to play an important role in cancer proliferation and metastasis. Recent studies have accumulated evidence that endocytosis inhibitors suppress in vitro and in vivo proliferation and migration. In addition, endocytosis inhibition has been shown to induce apoptosis, but its mechanism remains largely unclear. In this study, we found that the endocytosis inhibitor dynasore causes a cell viability reduction in multiple cancer cell lines, especially in hematopoietic cancers. Dynasore induced massive apoptosis and an S-phase progression delay. In addition, dynasore activated the ATR-Chk1 DNA damage response, which suggests a single-stranded DNA exposure induced by DNA replication stress. Furthermore, an ATR inhibitor sensitized the dynasore-induced apoptosis. These findings suggest that endocytosis inhibitors may have an ability to suppress DNA replication, a common mechanism of genotoxic chemotherapies targeting cancer, and that the anti-cancer effects of endocytosis inhibitors may be sensitized by DNA damage response inhibitors.
Volume 645
Pages 1-9
Published 2023-2-19
DOI 10.1016/j.bbrc.2023.01.035
PII S0006-291X(23)00066-9
PMID 36657293
MeSH Apoptosis* Ataxia Telangiectasia Mutated Proteins / metabolism Cell Line Checkpoint Kinase 1 / metabolism DNA Damage* Endocytosis
IF 2.985
Human and Animal Cells Jurkat(RCB0806)