Zoledronic acid is synergic with vinblastine to induce apoptosis in a multidrug resistance protein-1 dependent way: an in vitro study.

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Yildiz M, Celik-Ozenci C, Akan S, Akan I, Sati L, Demir R, Savas B, Ozben T, Samur M, Ozdogan M, Artac M, Bozcuk H

Zoledronic acid is synergic with vinblastine to induce apoptosis in a multidrug resistance protein-1 dependent way: an in vitro study.

Cell Biol Int. 2006 Mar;30(3):278-82. Epub 2006 Feb 2.

PubMed ID

16458542 [ View in PubMed

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Abstract

We have explored the action of zoledronic acid, which has an apoptotic effect and is used as an agent for treating skeletal metastases and osteoporosis, in the presence of vinblastine, and whether this effect is associated with MRP-1 (multidrug resistance protein-1) expression. HEK (human embryonic kidney) 293 cells were transfected to form the multidrug resistant cell line designated 293MRP (MRP-1 expressing HEK293 cells). Both lines were treated with varying concentrations of vinblastine and zoledronic acid. Apoptosis was determined by the TUNEL (deoxyuridine triphosphate nick end-labeling) method. The type of treatment, MRP-1 expression status, and the type of treatment with respect to MRP-1 expression status significantly affected (P < 0.001) the degree of apoptosis. The largest increase in cytotoxicity was noted in HEK293 cells, when 100 micromol zoledronic acid was added to 4 microg/ml vinblastine (an increment of 80.3%, P < 0.001). This preliminary work shows that zoledronic acid acts synergistically with vinblastine to induce apoptosis in an MRP-1 dependent way.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Vinblastine	Multidrug resistance-associated protein 1	Protein	Humans	Unknown	Substrate Inhibitor Inducer	Details
Zoledronic acid	Multidrug resistance-associated protein 1	Protein	Humans	Unknown	Substrate	Details