title: Dramatic synergistic anticancer effect of clinically achievable doses of lovastatin and troglitazone.
abstract: Lovastatin (an HMG-CoA reductase inhibitor) and troglitazone (a PPAR-gamma 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 p27(Kip1), 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.
authors.affiliation: Division of Cancer Research, National Health Research Institutes, Taipei, Taiwan.
authors.forename: Chih-Jung
authors.initials: CJ
authors.lastname: Yao
authors.forename: Gi-Ming
authors.initials: GM
authors.lastname: Lai
authors.forename: Chin-Feng
authors.initials: CF
authors.lastname: Chan
authors.forename: Ann-Lii
authors.initials: AL
authors.lastname: Cheng
authors.forename: Ya-Yu
authors.initials: YY
authors.lastname: Yang
authors.forename: Shuang-En
authors.initials: SE
authors.lastname: Chuang
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects*; D002839:Chromans / Q000008:administration & dosage; D019925:Cyclin A / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D050687:E2F1 Transcription Factor / Q000378:metabolism; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008148:Lovastatin / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D045162:Thiazolidinediones / Q000008:administration & dosage; D000077288:Troglitazone; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D002839:Chromans; D019925:Cyclin A; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D016160:Retinoblastoma Protein; D045162:Thiazolidinediones; D050760:Cyclin-Dependent Kinase Inhibitor p27; D008148:Lovastatin; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D000077288:Troglitazone