Vinorelbine induces apoptosis and caspase-3 (CPP32) expression in leukemia and lymphoma cells: a comparison with vincristine.
Vinorelbine (NVB) is a novel vinca alkaloid FDA approved for use in some advanced carcinomas. However, its role in non-Hodgkin's lymphoma (NHL) is still not well defined. NVB is an antimicrotubule agent, but as yet, it is not known whether it induces apoptosis. By flow cytometry using nuclear staining (propidium iodide) and annexin V, we demonstrated that NVB and vincristine (VCR) induced both mitotic arrest and apoptosis in leukemia and lymphoma cells, in a drug exposure time dependent manner. Cell cycle kinetics in 3 different cell lines varied during vinca alkaloid treatment. The annexin V method showed that apoptosis, as opposed to necrosis, was the dominant mode of cell kill of chemosensitive leukemia and lymphoma cells. Phosphatidylserine expression on the cell surface was detectable as a hallmark of apoptosis at earlier drug exposure when compared to conventional flow cytometry with PI staining. By Western blot analysis, we demonstrated that CPP32 or caspase-3, a critical apoptosis inducer, and its active subunits p20 and p11 were upregulated in chemo- and apoptosis-sensitive lymphoma and leukemia cells treated with NVB. Our data contributes to the emerging hypothesis suggesting that widely divergent exogenous stimuli and chemotherapeutic agents can effect apoptosis in cancer cells via different pathways involving the caspases. We believe that vinorelbine may be a potentially important drug in the treatment of NHL in the future.
Toh
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HC
Department of Medical Oncology, Singapore General Hospital, Singapore. HCToh@att.net
Sun
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Koh
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Aw
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D017304:Annexin A5 / Q000032:analysis; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000096:biosynthesis*; D002453:Cell Cycle / Q000187:drug effects; D004790:Enzyme Induction; D005434:Flow Cytometry; D006801:Humans; D015458:Leukemia, T-Cell / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014750:Vincristine / Q000627:therapeutic use*; D000077235:Vinorelbine
D017304:Annexin A5; D000972:Antineoplastic Agents, Phytogenic; D014750:Vincristine; D014747:Vinblastine; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D000077235:Vinorelbine