Selective blockade of T-type Ca2+ channels suppresses human breast cancer cell proliferation

• Published in: Cancer letters Vol. 267; no. 1; pp. 116 - 124
• Main Authors: Taylor, James T, Huang, Luping, Pottle, Jonathan E, Liu, Kai, Yang, Yali, Zeng, Xiangbin, Keyser, Brian M, Agrawal, Krishna C, Hansen, J. Bondo, Li, Ming
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Limited 18.08.2008
• Subjects: Benzimidazoles - pharmacology; Breast - drug effects; Breast - metabolism; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Calcium Channel Blockers - pharmacology; Calcium Channels, T-Type - metabolism; Cell cycle; Cell growth; Cell Line; Cell Proliferation - drug effects; Cyclopropanes; Hematology, Oncology and Palliative Medicine; Humans; Kinases; Naphthalenes; RNA, Small Interfering - pharmacology; Rodents; Breast cancer; siRNA; NNC-55-0396; Proliferation; T-type calcium channel
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2008.03.032

Abstract We have measured the expression of T-type Ca2+ channel mRNA in breast cancer cell lines (MCF-7 (ERα+) using Western blot and quantitative real-time PCR (Q-RT-PCR). These results revealed that the MCF-7 cells express both α1G and α1H isoforms of T-type Ca2+ channels. In order to further clarify the role of T-type Ca2+ channels in proliferation, we tested the effects of a selective T-type Ca2+ channel inhibitor NNC-55-0396 on cellular proliferation. MCF-7 (ERα+) cellular proliferation was inhibited by the compound. In contrast, NNC-55-0396 at same concentration had no effect on the proliferation of MCF-10A cells, a non-cancer breast epithelial cell line. We also found that message expression of the T-type Ca2+ channels were only expressed in rapidly growing non-confluent cells but not in the cytostatic confluent cells. Knocking down the expression of T-type Ca2+ channels with siRNA targeting both α1G and α1H resulted in growth inhibition as much as 45% ± 5.0 in MCF-7 cells as compared to controls. In conclusion, our results suggest that T-type Ca2+ channel antagonism/silencing may reduce cellular proliferation in mitogenic breast cells.