Histamine H{sub 3} receptor antagonist OUP-186 attenuates the proliferation of cultured human breast cancer cell lines
Histamine is involved in various physiological functions, including its neurotransmitter actions in the central nervous system and its action as a causative agent of inflammation, allergic reactions, and gastric acid secretions. Histamine expression and biosynthesis have been detected in breast cancer cells. It was recently suggested that the histamine H{sub 3} receptor (H{sub 3}R) plays a role in the proliferation of breast cancer cells. We recently developed the non-imidazole H{sub 3}R antagonist OUP-186 which exhibited a potent and selective human H{sub 3}R antagonistic activity as well as no activity against the human histamine H{sub 4} receptor (H{sub 4}R). In this study, we compared the effects of OUP-186 on the proliferation of estrogen receptor negative (ER−) breast cancer cells (MDA-MB-231) and ER+ breast cancer cells (MCF7) to the effects of clobenpropit (potent imidazole-containing H{sub 3}R antagonist). OUP-186 and clobenpropit suppressed the proliferation of breast cancer cells. The IC{sub 50} values at 48 h for OUP-186 and clobenpropit were approximately 10 μM and 50 μM, respectively. Furthermore, OUP-186 potently induced cell death by activating caspase-3/7, whereas cell death was only slightly induced by clobenpropit. In addition, OUP-186 treatment blocked the proliferation increase triggered by 100 μM (R)-(-)-α-methylhistamine (H{sub 3}R agonist). The use of 4-methylhistamine (H{sub 4}R agonist) and JNJ10191584 (selective H{sub 4}R antagonist) did not affect breast cancer proliferation. These results indicate that OUP-186 potently suppresses proliferation and induces caspase-dependent apoptotic death in both ER+ and ER-breast cancer cells. - Highlights: • OUP-186, a histamine H{sub 3} receptor antagonist, effects breast cancer cell growth. • OUP-186 potently suppressed proliferation and induced caspase-dependent apoptosis. • OUP-186 may be an effective drug against ER+ and ER− breast cancers.
- OSTI ID:
- 22696702
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 480, Issue 3; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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