title: Differential and kinetic effects of cell cycle inhibitors on neoplastic and primary astrocytes.
abstract: Alterations in cell cycle regulation underlie the unrestricted growth of neoplastic astrocytes. Chemotherapeutic interventions of gliomas have poor prognostic outcomes due to drug resistance and drug toxicity. Here, we examined the in vitro growth kinetics of C6 glioma (C6G) cells and primary astrocytes and their responses to 2 phase-specific inhibitors, lovastatin and hydroxyurea. C6G cells demonstrated a shorter G1phase and an earlier peak of DNA synthesis in S phase than primary astrocytes. As C6G cells and primary astrocytes re-entered the cell cycle in the presence of lovastatin or hydroxyurea, they exhibited different sensitivities to the inhibitory effects of these agents, as measured by [3H]-thymidine incorporation. Compared to primary astrocytes, C6G cells were more sensitive to lovastatin, but less sensitive to hydroxyurea. Studies using 2 different paradigms of exposure uncovered dramatic differences in the kinetics of DNA synthesis inhibition by these 2 agents in C6G cells and primary astrocytes. One notable difference was the ability of C6G cells to more easily recover from the inhibitory effects of hydroxyurea following short exposure. Our results provide insight into C6 glioma drug resistance as well as the inhibitory effects of these 2 phase-specific inhibitors and their chemotherapeutic potential.
authors: a Department of Neurosurgery , Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo , Buffalo , New York , USA.
authors: Veetai
authors: V
authors: Li
authors: b Department of Neurology , Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo , Buffalo , New York , USA.|c Department of Pediatrics , Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo , Buffalo , New York , USA.|d Department of Physiology and Biophysics of Medicine and Biomedical Sciences , State University of New York at Buffalo , Buffalo , New York , USA.|e Hunter James Kelly Research Institute, Jacobs School of Medicine and Biomedical Sciences, State University of New York at Buffalo , Buffalo , New York , USA.
authors: Thomas J
authors: TJ
authors: Langan
authors: f Department of Medicine , Geisel School of Medicine at Dartmouth , Lebanon , New Hampshire , USA.
authors: Kyla R
authors: KR
authors: Rodgers
authors: f Department of Medicine , Geisel School of Medicine at Dartmouth , Lebanon , New Hampshire , USA.
authors: Richard C
authors: RC
authors: Chou
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D006918:Hydroxyurea / Q000494:pharmacology; D007700:Kinetics; D008148:Lovastatin / Q000494:pharmacology; D009369:Neoplasms / Q000473:pathology*; D017207:Rats, Sprague-Dawley; D044967:Serum
chemical_list: D004247:DNA; D008148:Lovastatin; D006918:Hydroxyurea
keywords: C6 glioma; astrocytes; cell cycle inhibitors; hydroxyurea; lovastatin