RRC ID 64631
Author Suzuki S, Okada M, Kuramoto K, Takeda H, Sakaki H, Watarai H, Sanomachi T, Seino S, Yoshioka T, Kitanaka C.
Title Aripiprazole, an Antipsychotic and Partial Dopamine Agonist, Inhibits Cancer Stem Cells and Reverses Chemoresistance.
Journal Anticancer Res
Abstract BACKGROUND:There is a growing interest in repurposing antipsychotic dopamine antagonists for cancer treatment; however, antipsychotics are often associated with an increased risk of fatal events. The anticancer activities of aripiprazole, an antipsychotic drug with partial dopamine agonist activity and an excellent safety profile, remain unknown.
MATERIALS AND METHODS:The effects of aripiprazole alone or in combination with chemotherapeutic agents on the growth, sphere-forming ability and stem cell/differentiation/chemoresistance marker expression of cancer stem cells, serum-cultured cancer cells from which they were derived, and normal cells were examined.
RESULTS:At concentrations non-toxic to normal cells, aripiprazole inhibited the growth of serum-cultured cancer cells and cancer stem cells. Furthermore, aripiprazole induced differentiation and inhibited sphere formation, as well as stem cell marker expression of cancer stem cells while inhibiting their survivin expression and sensitizing them to chemotherapeutic agents.
CONCLUSION:Repurposing aripiprazole as an anticancer stem cell drug may merit further consideration.
Volume 36(10)
Pages 5153-5161
Published 2016-10-1
DOI 10.21873/anticanres.11085
PII 36/10/5153
PMID 27798875
MeSH Animals Antineoplastic Agents / pharmacology* Antipsychotic Agents / pharmacology Aripiprazole / pharmacology* Cell Differentiation / drug effects Cell Line, Tumor Cell Survival / drug effects Cells, Cultured Dopamine Agonists / pharmacology Drug Repositioning Drug Resistance, Neoplasm / drug effects* Fibroblasts / drug effects Humans Inhibitor of Apoptosis Proteins / metabolism Neoplastic Stem Cells / drug effects* Neural Stem Cells / drug effects Rats Survivin
IF 1.994
Human and Animal Cells A549(RCB0098)