Aripiprazole, an Antipsychotic and Partial Dopamine Agonist, Inhibits Cancer Stem Cells and Reverses Chemoresistance

• Published in: Anticancer research Vol. 36; no. 10; pp. 5153 - 5161
• Main Authors: Suzuki, Shuhei, Okada, Masashi, Kuramoto, Kenta, Takeda, Hiroyuki, Sakaki, Hirotsugu, Watarai, Hikaru, Sanomachi, Tomomi, Seino, Shizuka, Yoshioka, Takashi, Kitanaka, Chifumi
• Format: Journal Article
• Language: English
• Published: Greece 01.10.2016
• Subjects: 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; Drug repositioning; self-renewal capacity; mental illnesses; drug resistance; chemotherapy; psychiatric disorders
• ISSN: 0250-7005; 1791-7530
• DOI: 10.21873/anticanres.11085

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.