Establishment of a luciferase assay-based screening system: fumitremorgin C selectively inhibits cellular proliferation of immortalized astrocytes expressing an active form of AKT.
The AKT pathway is frequently activated in glioblastoma, and as such, inhibitors of this pathway could prove very useful as anti-glioblastoma therapies. Here we established immortalized astrocytes expressing Renilla luciferase as well as those expressing both an active form of AKT and firefly luciferase. Since both luciferase activities represent the numbers of corresponding cell lines, novel inhibitors of the AKT pathway can be identified by treating co-cultures containing the two types of luciferase-expressing cells with individual compounds. Indeed, such a screening system succeeded in identifying fumitremorgin C as an efficient inhibitor of the AKT pathway, which was further confirmed by the ability of fumitremorgin C to selectively inhibit the growth of immortalized astrocytes expressing an active form of AKT. The present study proposes a broadly applicable approach for identifying therapeutic agents that target the pathways and/or molecules responsible for cancer development.
Laboratory of Molecular and Cellular Pathology, Hokkaido University Graduate School of Medicine, N15 W7, Kita-ku, Sapporo 060-8638, Japan.
Lei
L
Wang
Ken
K
Sasai
Tsuyoshi
T
Akagi
Shinya
S
Tanaka
D000818:Animals; D000970:Antineoplastic Agents / Q000302:isolation & purification* / Q000494:pharmacology; D001253:Astrocytes / Q000201:enzymology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D049409:Luciferases, Firefly / Q000235:genetics; D049410:Luciferases, Renilla / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis / Q000235:genetics
D000970:Antineoplastic Agents; D007211:Indoles; D047428:Protein Kinase Inhibitors; C010522:tryptoquivaline; D049410:Luciferases, Renilla; D049409:Luciferases, Firefly; D051057:Proto-Oncogene Proteins c-akt