P21(WAF1/CIP1) is dispensable for G1 arrest, but indispensable for apoptosis induced by sodium butyrate in MCF-7 breast cancer cells.
Sodium butyrate (NaB) has been proposed as a potential anticancer agent. However, its mechanism of action is not totally elucidated. Here, we showed that NaB-induced cell cycle arrest and apoptosis were associated with an increase of P21(waf1/cip1) in MCF-7 breast cancer cells. This increase was more important in the nuclei, as revealed by immunofluorescence analysis. Transient transfections of MCF-7 cells with p21 deficient for interaction with CDK, but not with p21 deficient for interaction with PCNA (p21PCNA-), abrogated NaB-induced cell cycle arrest. This indicated that cell cycle blockage involved the interaction of P21(waf1/cip1) with CDK. However, P21(waf1/cip1) was dispensable, since p21 antisense did not modify cell cycle arrest. On the other hand, NaB-induced apoptosis was abolished by p21 antisense or p21PCNA-. In addition, NaB decreased PCNA levels, but increased the association of PCNA with P21(waf1/cip1). These results suggested that NaB-induced apoptosis required P21(waf1/cip1) and its interaction with PCNA.
Chopin
Valérie
V
Equipe facteurs de croissance, Laboratoire de Biologie du Développement (UPRES 1033), IFR 118, Université des Sciences et Technologies de Lille, Villeneuve d'Ascq Cedex 59655, France.
Toillon
Robert-Alain
RA
Jouy
Nathalie
N
Le Bourhis
Xuefen
X
D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology; D002087:Butyrates / Q000494:pharmacology*; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D016213:Cyclins / Q000032:analysis / Q000502:physiology*; D004260:DNA Repair; D005260:Female; D016193:G1 Phase / Q000187:drug effects*; D006801:Humans; D010957:Plasmids; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis
D002087:Butyrates; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D018809:Proliferating Cell Nuclear Antigen; D018844:Cyclin-Dependent Kinases