Shuhei Suzuki1,2, Masashi Okada3, Kenta Kuramoto1, Hiroyuki Takeda1,2, Hirotsugu Sakaki1,4, Hikaru Watarai1,5, Tomomi Sanomachi1, Shizuka Seino1,6, Takashi Yoshioka2, Chifumi Kitanaka3,6. 1. Department of Molecular Cancer Science, Yamagata University School of Medicine, Yamagata, Japan. 2. Department of Clinical Oncology, Yamagata University School of Medicine, Yamagata, Japan. 3. 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. 4. Department of Obstetrics and Gynecology, Yamagata University School of Medicine, Yamagata, Japan. 5. Second Department of Surgery, Yamagata University School of Medicine, Yamagata, Japan. 6. Research Institute for Promotion of Medical Sciences, Yamagata University Faculty of Medicine, Yamagata, Japan.
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. Copyright
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. Copyright
Authors: Jillian S Weissenrieder; Jeffrey D Neighbors; Richard B Mailman; Raymond J Hohl Journal: J Pharmacol Exp Ther Date: 2019-04-18 Impact factor: 4.030