title: Aripiprazole, an Antipsychotic and Partial Dopamine Agonist, Inhibits Cancer Stem Cells and Reverses Chemoresistance.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Repurposing aripiprazole as an anticancer stem cell drug may merit further consideration.
authors: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan.|Department of Clinical Oncology, Yamagata University School of Medicine, Yamagata, Japan.
authors: Shuhei
authors: S
authors: Suzuki
authors: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan m-okada@med.id.yamagata-u.ac.jp ckitanak@med.id.yamagata-u.ac.jp.
authors: Masashi
authors: M
authors: Okada
authors: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan.
authors: Kenta
authors: K
authors: Kuramoto
authors: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan.|Department of Clinical Oncology, Yamagata University School of Medicine, Yamagata, Japan.
authors: Hiroyuki
authors: H
authors: Takeda
authors: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan.|Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata, Japan.
authors: Hirotsugu
authors: H
authors: Sakaki
authors: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan.|Second Department of Surgery, Yamagata University School of Medicine, Yamagata, Japan.
authors: Hikaru
authors: H
authors: Watarai
authors: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan.
authors: Tomomi
authors: T
authors: Sanomachi
authors: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan.|Research Institute for Promotion of Medical Sciences, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors: Shizuka
authors: S
authors: Seino
authors: Department of Clinical Oncology, Yamagata University School of Medicine, Yamagata, Japan.
authors: Takashi
authors: T
authors: Yoshioka
authors: Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan m-okada@med.id.yamagata-u.ac.jp ckitanak@med.id.yamagata-u.ac.jp.|Research Institute for Promotion of Medical Sciences, Yamagata University Faculty of Medicine, Yamagata, Japan.
authors: Chifumi
authors: C
authors: Kitanaka
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology; D000068180:Aripiprazole / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018491:Dopamine Agonists / Q000494:pharmacology; D058492:Drug Repositioning; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D058953:Neural Stem Cells / Q000187:drug effects; D051381:Rats; D000077022:Survivin
chemical_list: D000970:Antineoplastic Agents; D014150:Antipsychotic Agents; C107489:BIRC5 protein, human; D018491:Dopamine Agonists; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D000068180:Aripiprazole
keywords: Drug repositioning; chemotherapy; drug resistance; mental illnesses; psychiatric disorders; self-renewal capacity