Novel dual-reporter preclinical screen for antiastrocytoma agents identifies cytostatic and cytotoxic compounds.
Astrocytoma/glioblastoma is the most common malignant form of brain cancer and is often unresponsive to current pharmacological therapies and surgical interventions. Despite several potential therapeutic agents against astrocytoma and glioblastoma, there are currently no effective therapies for astrocytoma, creating a great need for the identification of effective antitumor agents. The authors have developed a novel dual-reporter system in Trp53/Nf1-null astrocytoma cells to simultaneously and rapidly assay cell viability and cell cycle progression as evidenced by activity of the human E2F1 promoter in vitro. The dual-reporter high-throughput assay was used to screen experimental therapeutics for activity in Trp53/Nf1-null astrocytoma. Several compounds were identified demonstrating selectivity for astrocytoma over primary astrocytes. The dual-reporter system described here may be a valuable tool for identifying potential antitumor treatments that specifically target astrocytoma.
Hawes
Jessica J
JJ
Mouse Cancer Genetics Program, National Cancer Institute, Frederick, Maryland 21702, USA.
Nerva
John D
JD
Reilly
Karlyne M
KM
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use; D001254:Astrocytoma / Q000188:drug therapy*; D002166:Camptothecin / Q000627:therapeutic use; D054697:Cytostatic Agents / Q000627:therapeutic use*; D003603:Cytotoxins / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D017930:Genes, Reporter; D006801:Humans; D015739:Nocodazole / Q000627:therapeutic use; D015203:Reproducibility of Results
D000970:Antineoplastic Agents; D054697:Cytostatic Agents; D003603:Cytotoxins; D015739:Nocodazole; D002166:Camptothecin