Nitrogen-containing bisphosphonate incadronate augments the inhibitory effect of farnesyl transferase inhibitor tipifarnib on the growth of fresh and cloned myeloma cells in vitro.
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.
Ochiai
Naoya
N
Division of Hematology and Oncology, Department of Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan. naoya@koto.kpu-m.ac.jp
Yamada
Noriko
N
Uchida
Ryo
R
Fuchida
Shin-Ichi
S
Okano
Akira
A
Okamoto
Masashi
M
Ashihara
Eishi
E
Inaba
Tohru
T
Shimazaki
Chihiro
C
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
D004164:Diphosphonates; D015363:Quinolones; C071542:cimadronate; D051231:Farnesyltranstransferase; C402769:tipifarnib