Pectenotoxin-2 induces G2/M phase cell cycle arrest in human breast cancer cells via ATM and Chk1/2-mediated phosphorylation of cdc25C.
Although pectenotoxin-2 (PTX-2) is known to regulate the actin depolymerization and to induce apoptosis through downregulation of telomerase activity, little is known on its effect on the cell cycle regulation. Therefore, we investigated the effects of PTX-2 on G2/M arrest in human breast cancer cells (MDA-MB-231 and MCF-7). Treatment with PTX-2 significantly suppressed cell proliferation and induced G2/M phase arrest through down-regulation of cyclin B1 and cdc2 expression, but also through phosphorylation of cdc25C. We found increased phosphorylation of ATM and Chk1/2 in a PTX-2 dose-dependent manner. Furthermore, treatment with PTX-2 increased H2O2 generation with correlated G2/M arrest. Our results showed that ATM- and Chk1/2-mediated phosphorylation of cdc25C plays a major role in G2/M arrest, but not in H2O2 generation induced by PTX-2 treatment. We also observed that PTX-2-induced cell cycle arrest was not restricted to p53 status in human breast cancer cells.
Moon
Dong-Oh
DO
Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea.
Kim
Mun-Ock
MO
Nam
Taek-Jeong
TJ
Kim
Se-Kwon
SK
Choi
Yung Hyun
YH
Kim
Gi-Young
GY
D000970:Antineoplastic Agents / Q000494:pharmacology; D064007:Ataxia Telangiectasia Mutated Proteins; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D005260:Female; D005663:Furans / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D018942:Macrolides; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D011494:Protein Kinases / Q000378:metabolism / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology; D011714:Pyrans / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects; D020687:cdc25 Phosphatases / Q000378:metabolism*; D000095702:Polyether Toxins
D000970:Antineoplastic Agents; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D004268:DNA-Binding Proteins; D005663:Furans; D018942:Macrolides; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011714:Pyrans; D025521:Tumor Suppressor Proteins; D020687:cdc25 Phosphatases; C098380:pectenotoxin 2; D000095702:Polyether Toxins; C576324:ATM protein, human; C000605867:CHEK1 protein, human; C578634:CHEK2 protein, human; C517009:CDC25C protein, human