title: Effect of farnesyl transferase inhibitor R115777 on the growth of fresh and cloned myeloma cells in vitro.
abstract: Ras gene mutations occur in 30% to 40% of patients with multiple myeloma (MM), and farnesylation is the first and most important step in the posttranslational modification of Ras proteins. R115777 is a newly synthesized potent farnesyl transferase inhibitor (FTI) and has recently demonstrated significant antitumor activities in vitro and in vivo. Therefore, we examined the effect of R115777 on the growth of fresh and cloned myeloma cells in vitro. R115777 inhibited the growth of fresh and cloned myeloma cells dose dependently, and effects were not dependent on the status of N-Ras mutation in fresh myeloma cells. Flow cytometric analysis using annexin V and 7-aminoactinomycin D (7AAD) showed that R115777 induced apoptosis of 2 of 3 myeloma cell lines at a concentration of 1.0 x 10(-8) M. R115777 appears to be a potent inducer of apoptosis, and its effects depend on the status of Ras mutation in cloned myeloma cells but not on the status of N-Ras mutation in fresh myeloma cells. This is the first report that demonstrates the relationship between the N-Ras mutation in fresh myeloma cells and the effect of R115777. R115777 might have some benefit in the treatment of myeloma patients.
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan. naoya@koto.kpu-m.ac.jp
authors.forename: Naoya
authors.initials: N
authors.lastname: Ochiai
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: Naohisa
authors.initials: N
authors.lastname: Fujita
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsubara
authors.forename: Chihiro
authors.initials: C
authors.lastname: Shimazaki
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002455:Cell Division; D045744:Cell Line, Tumor; D002469:Cell Separation; D004305:Dose-Response Relationship, Drug; D051231:Farnesyltranstransferase; D006801:Humans; D009101:Multiple Myeloma / Q000473:pathology*; D009154:Mutation; D015363:Quinolones / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D018631:ras Proteins / Q000235:genetics / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D015363:Quinolones; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; D018631:ras Proteins; C402769:tipifarnib