Potentiation by tumor necrosis factor of mitoxantrone cytotoxicity to human ovarian cancer cell lines.
The cytotoxic activity of human recombinant tumor necrosis factor (rHuTNF) (from 0.01 to 10000 U/ml) was assayed on six human ovarian cancer cell lines and one human cervical carcinoma cell line using a crystal violet assay. rHuTNF was cytotoxic to four cell lines (A2780, A2774, SW626, PA1), while 3 cell lines (IGROV1, SKOV3, Me180) were marginally sensitive to its activity. However, under the same experimental conditions rHuTNF markedly enhanced the cytotoxicity of mitoxantrone, a chemotherapeutic drug targeted at DNA topoisomerase II, in six cell lines. The potentiation of mitoxantrone cytotoxicity was not caused by increased drug accumulation after rHuTNF treatment. No significant increase in cytotoxicity to Me180 cell line was seen when rHuTNF was added to mitoxantrone.
Russo
P
P
Department of Chemical Carcinogenesis, Istituto Nazionale per 1a Ricerca sul Cancro, Genova, Italy.
Parodi
S
S
Billi
G
G
Oliva
C
C
Venturini
M
M
Noviello
E
E
Conte
P
P
D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008942:Mitoxantrone / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D008942:Mitoxantrone