Cyclin B1 depletion inhibits proliferation and induces apoptosis in human tumor cells.
Cyclin B1 is the regulatory subunit of M-phase promoting factor, and proper regulation of cyclin B1 is essential for the initiation of mitosis. Increasing evidence indicates that the deregulation of cyclin B1 is involved in neoplastic transformation, suggesting the suppression of cyclin B1 could be an attractive strategy for antiproliferative therapy. In the present work, we analysed the impact of small interfering RNAs (siRNAs) targeted to cyclin B1 on different human tumor cell lines. Cyclin B1 siRNAs reduced the protein level of cyclin B1 in HeLa, MCF-7, BT-474 and MDA-MB-435 tumor cells and efficiently reduced the kinase activity of Cdc2/cyclin B1 in HeLa cells. siRNA-treated cells were arrested in G2/M phase in all tumor cell lines tested. Proliferation of tumor cells from different origins was suppressed by 50-80% 48 h after transfection and apoptosis was increased from 5 to 40-50%. Furthermore, tumor cells showed less colony-forming ability after siRNA treatment. In contrast, primary human umbilical vein endothelial cells exhibited only a slight change in cell cycle, and neither apoptosis nor clear inhibition of proliferation was observed after cyclin B1 siRNA treatment for 48 h. These results indicate that siRNAs against cyclin B1 could become a powerful antiproliferative tool in future antitumor therapy.
Yuan
Juping
J
Department of Gynaecology and Obstetrics, Medical School, JW Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany.
Yan
Ruilan
R
Krämer
Andrea
A
Eckerdt
Frank
F
Roller
Marc
M
Kaufmann
Manfred
M
Strebhardt
Klaus
K
D017209:Apoptosis / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D016203:CDC2 Protein Kinase / Q000187:drug effects / Q000378:metabolism; D002455:Cell Division / Q000235:genetics; D002478:Cells, Cultured; D019926:Cyclin B / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D056744:Cyclin B1; D015536:Down-Regulation; D005260:Female; D016195:G2 Phase / Q000187:drug effects / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D016200:Maturation-Promoting Factor / Q000187:drug effects / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects / Q000235:genetics; D014411:Neoplastic Stem Cells; D034741:RNA, Small Interfering / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins / Q000166:cytology
C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D034741:RNA, Small Interfering; D016203:CDC2 Protein Kinase; D016200:Maturation-Promoting Factor