In vitro enhancement of cis-platinum antitumor activity by caffeine and pentoxifylline in a human ovarian cell line.
Cell kinetic perturbations measuring DNA and nuclear protein with dual-parameter flow cytometry were studied in vitro after cis-platinum (DDP) treatment of a DDP-resistant human ovarian cell line (BG-1). Cell viability (trypan blue exclusion) and the cell's ability to replicate (replicating potential) are also reported. A dose-dependent G2 arrest and concomitant increase in cytotoxicity were observed. We also observed a marked increase in cytotoxicity of 2.5 micrograms/ml DDP with the addition of 1 mM of caffeine (CAF) or pentoxifylline (PTX). Additionally, the cells treated with DDP and CAF or DDP and PTX demonstrated a markedly diminished ability to replicate. Cell cycle perturbations, especially the G2-phase arrest, were markedly enhanced in the cells treated with DDP and CAF or DDP and PTX, when compared to that in cells treated with DDP alone. We conclude that the cytotoxicity of DDP is enhanced by CAF and PTX in vitro by inhibiting DNA repair during the S and G2 phases.
Schiano
M A
MA
Department of Obstetrics and Gynecology, University of Miami School of Medicine, Florida 33101.
Sevin
B U
BU
Perras
J
J
Ramos
R
R
Wolloch
E H
EH
Averette
H E
HE
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002110:Caffeine / Q000008:administration & dosage / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000032:analysis; D004357:Drug Synergism; D005260:Female; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D009363:Neoplasm Proteins / Q000032:analysis; D009687:Nuclear Proteins / Q000032:analysis; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010431:Pentoxifylline / Q000008:administration & dosage / Q000494:pharmacology*; D014343:Trypan Blue; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D002110:Caffeine; D014343:Trypan Blue; D002945:Cisplatin; D010431:Pentoxifylline