Carboxyamido-triazole inhibits proliferation of human breast cancer cells via G(2)/M cell cycle arrest and apoptosis.
Carboxyamido-triazole (CAI), a voltage-independent calcium channel inhibitor, has been shown to be able to induce growth inhibition and apoptosis in cancer cells. In the present study, we demonstrate that CAI significantly inhibits proliferation of cultured MCF-7 human breast cancer cells in a dose-dependent manner with an IC(50) of approximately 26 microM. Reduced proliferation of MCF-7 cells in the presence of CAI correlated with accumulation of cells in G(2)/M phase and induction of apoptosis. A treatment of MCF-7 cells with 30 microM CAI caused a time-dependent decrease in the levels of proteins that regulate G(2)/M progression, including Cdk1, Cyclin B1, and Cdc25C. A simultaneous increase in the expression of p21 protein was observed. We also demonstrated a concurrent decrease of the mitochondrial membrane potential (DeltaPsi(m)), and down-regulation of anti-apoptotic protein Bcl-2. In conclusion, it seems reasonable to hypothesize that the antitumor effect of CAI in MCF-7 cells is based on G(2)/M cell cycle arrest and inducing apoptosis.
Guo
Lei
L
Department of Pharmacology, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
Li
Zhi-Song
ZS
Wang
Hong-Ling
HL
Ye
Cai-Ying
CY
Zhang
De-Chang
DC
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology*
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D019253:Proto-Oncogene Proteins c-bcl-2; D014230:Triazoles; C062058:carboxyamido-triazole