Vinorelbine (VNR) is a semi-synthetic vinca alkaloid known to exert its antitumour activity by interfering with the polymerisation of tubulin. It has shown a broad spectrum of activity in some advanced carcinomas including lung, breast and ovary. This report demonstrates for the first time the antiproliferative effect of VNR and its molecular mechanism in human osteosarcoma in vitro. TP53 wild type HOS cells and TP53 mutated MG-63 cells were chosen for this study. VNR caused a significant dose and time dependent growth inhibition and induced apoptotic death in each cell line, independent of TP53 status. Phosphorylation and/or alteration of Bcl-2 were not induced here by VNR, thereby indicating a new pathway utilised by the drug to induce apoptosis in vitro. VNR produced a reduction of Cyclin D1 and an increase of p53 expression in TP53 wild type HOS cells, whereas no alteration in Cyclin D1 expression was evident in the TP53 negative MG-63 cells. These data suggest a new potential use for Vinorelbine as a therapeutic agent against human osteosarcoma.

Effect of Vinorelbine on cell growth and apoptosis induction in human osteosarcoma in vitro

RONCUZZI, LAURA;BAIOCCHI, DANIELA;COCCHI, STEFANIA;GASPERI CAMPANI, ANNA
2006

Abstract

Vinorelbine (VNR) is a semi-synthetic vinca alkaloid known to exert its antitumour activity by interfering with the polymerisation of tubulin. It has shown a broad spectrum of activity in some advanced carcinomas including lung, breast and ovary. This report demonstrates for the first time the antiproliferative effect of VNR and its molecular mechanism in human osteosarcoma in vitro. TP53 wild type HOS cells and TP53 mutated MG-63 cells were chosen for this study. VNR caused a significant dose and time dependent growth inhibition and induced apoptotic death in each cell line, independent of TP53 status. Phosphorylation and/or alteration of Bcl-2 were not induced here by VNR, thereby indicating a new pathway utilised by the drug to induce apoptosis in vitro. VNR produced a reduction of Cyclin D1 and an increase of p53 expression in TP53 wild type HOS cells, whereas no alteration in Cyclin D1 expression was evident in the TP53 negative MG-63 cells. These data suggest a new potential use for Vinorelbine as a therapeutic agent against human osteosarcoma.
Roncuzzi L; Marti G; Baiocchi D; Del Coco R; Cocchi S; Gasperi-Campani A
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11585/36463
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