title: Zoledronic acid is synergic with vinblastine to induce apoptosis in a multidrug resistance protein-1 dependent way: an in vitro study.
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.
authors.affiliation: Pamukkale University Medical Faculty, Department of Medical Oncology, Denizli, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Yildiz
authors.forename: Ciler
authors.initials: C
authors.lastname: Celik-Ozenci
authors.forename: Selma
authors.initials: S
authors.lastname: Akan
authors.forename: Ilhan
authors.initials: I
authors.lastname: Akan
authors.forename: Leyla
authors.initials: L
authors.lastname: Sati
authors.forename: Ramazan
authors.initials: R
authors.lastname: Demir
authors.forename: Burhan
authors.initials: B
authors.lastname: Savas
authors.forename: Tomris
authors.initials: T
authors.lastname: Ozben
authors.forename: Mustafa
authors.initials: M
authors.lastname: Samur
authors.forename: Mustafa
authors.initials: M
authors.lastname: Ozdogan
authors.forename: Mehmet
authors.initials: M
authors.lastname: Artac
authors.forename: Hakan
authors.initials: H
authors.lastname: Bozcuk
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D004164:Diphosphonates / Q000494:pharmacology*; D004357:Drug Synergism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D015151:Immunoblotting; D014747:Vinblastine / Q000494:pharmacology*; D000077211:Zoledronic Acid
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004164:Diphosphonates; D007093:Imidazoles; D014747:Vinblastine; D000077211:Zoledronic Acid