T-type calcium channel antagonists,mibefradil and NNC-55-0396 inhibit cell proliferation and induce cell apoptosis in leukemia cell lines

Background: t-type ca2+ channels are often aberrantly expressed in different human cancers and participate in the regulation of cell cycle progression,proliferation and death. methods: rt-pcr,q-pcr,western blotting and whole-cel patch-clamp recording were employed to assess the expression of t-type ca2+ channels in leukemia cell lines. the function of t-type ca2+ channels in leukemia cell growth and the possible mechanism of the effect of t-type ca2+ channel antagonists on cell proliferation and apoptosis were examined in t-lymphoma cell lines. results: we show that leukemia cell lines exhibited reduced cell growth when treated with t-type ca2+ channel inhibitors,mibefradil and nnc-55-0396 in a concentration-dependent manner. mechanistically,these inhibitors played a dual role on cell viability: (i) blunting proliferation,through a halt in the progression to the g1-s phase; and (ii) promoting cell apoptosis,partially dependent on the endoplasmic reticulum ca2+ release. in addition,we observed a reduced phosphorylation of erk1/2 in molt-4 cells in response to mibefradil and nnc-55-0396 treatment. conclusions: these results indicate that mibefradil and nnc-55-0396 regulate proliferation and apoptosis in t-type ca2+ channel expressing leukemia cell lines and suggest a potential therapeutic target for leukemia. © 2015 huang et al.; licensee biomed central.