Circumvention of atypical multidrug resistance with tumor necrosis factor.
Some "multidrug-resistant" (MDR) cell lines are not associated with a defect in drug accumulation or with the overexpression of P-glycoprotein. These cell lines are defined as "atypical MDR" (at-MDR) and they often express altered or mutated topoisomerase II. We investigated the ability of tumor necrosis factor to reverse at-MDR (in the human ovarian cancer cell line A2780 DX3) on the basis of its efficacy in potentiating in vitro topoisomerase II-targeted drugs, and because there is convincing evidence that the synergy is due to an increased number of topoisomerase-associated strand-breaks as well as to an increased level of extractable topoisomerase.
Cimoli
G
G
Department of Chemical Carcinogenesis, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Valenti
M
M
Parodi
S
S
De Sessa
F
F
Russo
P
P
D004249:DNA Damage; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D004351:Drug Resistance / Q000235:genetics / Q000502:physiology*; D004357:Drug Synergism; D005047:Etoposide / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008942:Mitoxantrone / Q000494:pharmacology / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured / Q000201:enzymology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D059005:Topoisomerase II Inhibitors; D014409:Tumor Necrosis Factor-alpha; D005047:Etoposide; D004317:Doxorubicin; D008942:Mitoxantrone; D004250:DNA Topoisomerases, Type II