title: T-type calcium channel antagonists, mibefradil and NNC-55-0396 inhibit cell proliferation and induce cell apoptosis in leukemia cell lines.
abstract: BACKGROUND
  T-type Ca(2+) 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-cell patch-clamp recording were employed to assess the expression of T-type Ca(2+) channels in leukemia cell lines. The function of T-type Ca(2+) channels in leukemia cell growth and the possible mechanism of the effect of T-type Ca(2+) 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 Ca(2+) 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 Ca(2+) 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 Ca(2+) channel expressing leukemia cell lines and suggest a potential therapeutic target for leukemia.
authors.affiliation: Fujian Institute of Hematology, Fujian Medical University Union Hospital, Fuzhou, 350004, People's Republic of China. hwf0625@163.com.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Blood Transfusion, Maternal and Child Health Hospital of Xiamen, Xiamen, 361003, People's Republic of China. 272828086@qq.com.
authors.forename: Chunjing
authors.initials: C
authors.lastname: Lu
authors.affiliation: Fujian Institute of Hematology, Fujian Medical University Union Hospital, Fuzhou, 350004, People's Republic of China. wuyong9195@126.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Xiamen Medical Research Institute, Xiamen, 361008, People's Republic of China. xmmri@xmu.edu.cn.
authors.forename: Shou
authors.initials: S
authors.lastname: Ouyang
authors.affiliation: Fujian Institute of Hematology, Fujian Medical University Union Hospital, Fuzhou, 350004, People's Republic of China. chenyz@mail.fjmu.edu.cn.
authors.forename: Yuanzhong
authors.initials: Y
authors.lastname: Chen
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020747:Calcium Channels, T-Type / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003521:Cyclopropanes / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020748:Mibefradil / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*
chemical_list: D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D003521:Cyclopropanes; D009281:Naphthalenes; C484287:NNC 55-0396; D020748:Mibefradil