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Roles of roscovitine and minosine in Fasmediated leukemia cell apoptosis and the possible mechanism
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Abstract:
Abstract Objective: To assess the roles of roscovitine (an inhibitor of DCK) and mimosine (DNA synthesis inhibitor) in Fasmediated leukemia cell apoptosis and to understand the possible mechanism. Methods: The target leukemia cell lines Molt4 and Jurkat were incubated with rhFasL, roscovitine and mimosine separately or with rhFasL+roscovitine or rhFasL+minosine for 18 h （Jurkat 8 h）, 24 h, and 24 h. Apoptotic cells were examined by Annexin V method or modified API method; cyclins expression were detected by cyclin/DNA biparameter flow cytometry; CDK1 and CDK2 activities were detected by Western blotting. Results: Fasmediated cell apoptosis was at G1 phase. Both roscovitine and mimosine significantly promoted Fasmediated apoptosis (P<0.05). Moreover, mimosine increased the levels of cycline D3 and cyclin E at G1 phase and more cells were arrested at G1phase; roscovitine also lowered the phosphorylation of CDK2 Thr160. Minosine+rhFasl decreased the phosphorylation of CDK2 Thr160, and the target cells were completely arrested at G1 phase; it also decreased the levels of cyclin D3, E, A and B1 and the phosphorylation of CDK2 Thr160 and CDK1 Thr161. Conclusion: Both roscovitine and mimosine have synergistic effects with rhFasL in inducing apoptosis of leukemia cells, which is related to the G1 phase cell arrest, inhibition of CKD2 activity and influence of cyclin proteins.
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Project Supported:
Supported by the Major State Basic Research Development Program of China(No. 2004CB518705); the National Natural Science Foundation of China(No. 30440024)
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