Cyclin B1 depletion inhibits proliferation and induces apoptosis in human tumor cells

Abstract

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 colonyforming 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.

Analysis of cyclin B1 and CDK activity during apoptosis induced by camptothecin treatment

“…We then tested the role of cyclin B1 and cyclin E1 directly by blocking the expression by RNAi. siRNA for cyclin B1 reduced the amount of cyclin B1 protein and reduced the number of cells in primary apoptosis at 24 and 48 h. It has been previously reported that reduction of cyclin B1 protein by RNAi (without further treatment with cytotoxic agents such as CPT) increases the percentage of cells in G2/M-phase and initiates apoptosis by 48 h (Yuan et al, 2004). In the results reported here, we also detected a cell cycle arrest and an increase in sub-G1 cells after siRNA treatment at 48 h ( Figure 6b).…”

Chk1-induced CCNB1 overexpression promotes cell proliferation and tumor growth in human colorectal cancer

“…19 CCNB1, the regulatory subunit of MPF, could specifically increases the activity of CDK1, further leading to a strong proliferation promotion in a variety of cancer cells. 10,20 Studies have also revealed that CCNB1 is highly expressed in various primary tumors, 5-9 including colorectal cancer. 21 These data highlight the potential pivotal roles of CCNB1 both in the development and progression of malignancy.…”

Cyclin B2 suppresses mitotic failure and DNA re-replication in human somatic cells knocked down for both cyclins B1 and B2

“…This has led to the idea that cyclin B2 could not compensate for a lack of cyclin B1. However, while cyclin B1 depletion by RNA interference in cultured cells has been shown to inhibit proliferation by arresting cells in G 2 /M, (Yuan et al, 2004(Yuan et al, , 2006, the degree of cell growth inhibition is dependent on the cell type and, surprisingly, human primary cells do not exhibit any defect, despite a quasi-complete inhibition of cyclin B1/CDK1 kinase activity (Yuan et al, 2004).…”