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Vinorelbine Increases the Progression to Apoptosis in Hl-60 Acute Promyelocytic Leukemia Cell Line

Sevilcan Tuna Gazi, Cem Gazi, Ercan Babur, Ayhan Bilir

Background

Vinorelbine is a semi-synthetic vinca alkaloid that has been employed both as a single agent and in combination, and has shown significant antitumor activity. Dexamethasone which acts on glucocorticoid and meperidine which acts on mu opioid receptors have pro-apoptotic and anti-proliferative effects. We investigated the effects of dexamethasone and meperidine on the cytotoxicity of vinorelbine on HL-60 human acute promyelocytic leukemia cell line.

Methods

The cytotoxic effects of vinorelbine alone and in combination with dexamethasone or meperidine were examined on the HL-60 cell line by performing plating efficacy, BrdU, caspase 3, bcl-2 immunocytochemistry and flow cytometry.

Results

We determined that vinorelbine inhibited cell proliferation and decreased the rate of synthase phase cells. Furthermore, by immunocytochemistry and flow cytometry analyzes we found that vinorelbine increased the rate of apoptotic cells via decreasing bcl-2 and increasing caspase-3 activation. No additive effects were observed when dexamethasone was combined with vinorelbine. However, meperidine increased the apoptotic effect of vinorelbine.

Conclusion

Vinorelbine promotes apoptosis in HL-60 cells and may be helpful in the treatment of acute promyelocytic leukemia patients. Moreover using meperidine with vinorelbine in the treatment may be beneficial.