Dramatic synergistic anticancer effect of clinically achievable doses of lovastatin and troglitazone
Journal
International Journal of Cancer
Journal Volume
118
Journal Issue
3
Pages
773-779
Date Issued
2006
Author(s)
Abstract
Lovastatin (an HMG-CoA reductase inhibitor) and troglitazone (a PPAR-γ agonist) have been intensively studied prospectively for their application in cancer treatment. However, clinical trials of lovastatin or troglitazone in cancer treatment resulted in only limited responses. To improve their efficacy, lovastatin and troglitazone have, respectively, been tried to combine with other anticancer agents with varied outcomes. In our study, we found a dramatic synergism between lovastatin and troglitazone in anticancer at clinically achievable concentrations. This synergism was found in far majority of cell lines tested including DBTRG 05 MG (glioblastoma) and CL1-0 (lung). This amazing synergism was accompanied by synergistic modulation of E2F-1 and p27Kip1, which were reported to mediate the anticancer activities of lovastatin and troglitazone, respectively, and other cell cycle regulating proteins such as CDK2, cyclin A and RB phosphorylation status. With this dramatic combination effect of lovastatin and troglitazone, a promising regimen of cancer therapy may be materialized in the future. ? 2005 Wiley-Liss, Inc.
Subjects
HMG-CoA reductase; Lovastatin; PPAR-gamma; Statin; Synergism; Troglitazone
SDGs
Other Subjects
ciglitazone; cyclin A; cyclin dependent kinase 2; hydroxymethylglutaryl coenzyme A reductase inhibitor; mevalonolactone; mevinolin; peroxisome proliferator activated receptor gamma agonist; protein p27; retinoblastoma protein; rosiglitazone; transcription factor E2F1; troglitazone; antineoplastic activity; article; cancer cell culture; cell cycle; controlled study; dose response; drug effect; drug potentiation; glioblastoma; human; human cell; lung cancer; pancreas cancer; priority journal; prostate cancer; protein phosphorylation; uterine cervix cancer; Western blotting; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Cell Survival; Chromans; Cyclin A; Cyclin-Dependent Kinase 2; Cyclin-Dependent Kinase Inhibitor p27; Dose-Response Relationship, Drug; Drug Synergism; E2F1 Transcription Factor; Glioblastoma; Hela Cells; Humans; Lovastatin; Lung Neoplasms; Male; Pancreatic Neoplasms; Phosphorylation; Prostatic Neoplasms; Retinoblastoma Protein; Thiazolidinediones; Tumor Cells, Cultured
Type
journal article