title: Nitrogen-containing bisphosphonate incadronate augments the inhibitory effect of farnesyl transferase inhibitor tipifarnib on the growth of fresh and cloned myeloma cells in vitro.
abstract: RAS gene mutations occur in 30 - 40% of multiple myeloma (MM) patients. Farnesylation is the first step in the post-translational modification of RAS proteins. Tipifarnib is a potent farnesyl transferase inhibitor, and incadronate prevents post-translational prenylation of GTP-binding proteins such as RAS proteins. We examined the effect of tipifarnib in combination with incadronate on the growth of fresh and cloned myeloma cells in vitro. Tipifarnib inhibited the growth of myeloma cells, and this inhibition was intensified when tipifarnib was combined with incadronate. Tipifarnib, in combination with incadronate, may have some benefits in MM patients.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. naoya@koto.kpu-m.ac.jp
authors.forename: Naoya
authors.initials: N
authors.lastname: Ochiai
authors.forename: Noriko
authors.initials: N
authors.lastname: Yamada
authors.forename: Ryo
authors.initials: R
authors.lastname: Uchida
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Fuchida
authors.forename: Akira
authors.initials: A
authors.lastname: Okano
authors.forename: Masashi
authors.initials: M
authors.lastname: Okamoto
authors.forename: Eishi
authors.initials: E
authors.lastname: Ashihara
authors.forename: Tohru
authors.initials: T
authors.lastname: Inaba
authors.forename: Chihiro
authors.initials: C
authors.lastname: Shimazaki
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis; D049109:Cell Proliferation / Q000187:drug effects*; D004164:Diphosphonates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy / Q000473:pathology*; D015363:Quinolones / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D004164:Diphosphonates; D015363:Quinolones; C071542:cimadronate; D051231:Farnesyltranstransferase; C402769:tipifarnib