Olanzapine, an Atypical Antipsychotic, Inhibits Survivin Expression and Sensitizes Cancer Cells to Chemotherapeutic Agents.

Abstract

BACKGROUND/AIM:

Olanzapine, an atypical antipsychotic, is now increasingly used as an off-label indication for the management of cancer patients with chemotherapy-induced nausea and vomiting (CINV). However, how olanzapine affects cancer cells per se remains poorly understood.

MATERIALS AND METHODS:

The effects of olanzapine treatment and survivin knockdown, alone or in combination with chemotherapeutic agents, on survivin expression and cell viability were investigated in human cancer cell lines.

RESULTS:

Olanzapine reduced survivin expression in lung and pancreatic cancer stem cell (CSC) lines and sensitized them to chemotherapeutic agents such as 5-fluorouracil, gemcitabine, and cisplatin in a survivin expression-dependent manner. Olanzapine also reduced survivin expression and chemosensitized serum-cultured, non-CSC ovarian cancer cells that expressed survivin.

CONCLUSION:

Olanzapine may benefit cancer patients not only as an antiemetic for CINV, but also by enhancing the effects of chemotherapeutic agents through down-regulation of survivin, which has been implicated in multidrug chemoresistance.

• Authors: Tomomi Sanomachi, Shuhei Suzuki, Kenta Kuramoto, Hiroyuki Takeda, Hirotsugu Sakaki, Keita Togashi, Shizuka Seino, Takashi Yoshioka, Masashi Okada, Chifumi Kitanaka
• Journal: Anticancer research (Anticancer Res) Vol. 37 Issue 11 Pg. 6177-6188 (11 2017) ISSN: 1791-7530 [Electronic] Greece
• PMID: 29061799 (Publication Type: Journal Article)
• Copyright: Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Antineoplastic Agents
• Antipsychotic Agents
• BIRC5 protein, human
• Inhibitor of Apoptosis Proteins
• Survivin
• Benzodiazepines
• Olanzapine

Topics

• Antineoplastic Agents (pharmacology)
• Antipsychotic Agents (pharmacology)
• Apoptosis (drug effects)
• Benzodiazepines (pharmacology)
• Cell Proliferation (drug effects)
• Drug Resistance, Neoplasm (drug effects)
• Humans
• Inhibitor of Apoptosis Proteins (antagonists & inhibitors)
• Lung Neoplasms (drug therapy, metabolism, pathology)
• Neoplastic Stem Cells (drug effects, metabolism, pathology)
• Olanzapine
• Pancreatic Neoplasms (drug therapy, metabolism, pathology)
• Survivin
• Tumor Cells, Cultured