Selective blockade of T-type Ca2+ channels suppresses human breast cancer cell proliferation.
We have measured the expression of T-type Ca2+ channel mRNA in breast cancer cell lines (MCF-7 (ERalpha+) using Western blot and quantitative real-time PCR (Q-RT-PCR). These results revealed that the MCF-7 cells express both alpha1G and alpha1H 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 (ERalpha+) 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 alpha1G and alpha1H 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.
Taylor
James T
JT
Department of Pharmacology, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
Huang
Luping
L
Pottle
Jonathan E
JE
Liu
Kai
K
Yang
Yali
Y
Zeng
Xiangbin
X
Keyser
Brian M
BM
Agrawal
Krishna C
KC
Hansen
J Bondo
JB
Li
Ming
M
D001562:Benzimidazoles / Q000494:pharmacology*; D001940:Breast / Q000187:drug effects / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D003521:Cyclopropanes; D006801:Humans; D009281:Naphthalenes; D034741:RNA, Small Interfering / Q000494:pharmacology
D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D003521:Cyclopropanes; D009281:Naphthalenes; D034741:RNA, Small Interfering; C484287:NNC 55-0396