Poly(ADP-ribose) polymerase-1 inhibitor 3-aminobenzamide enhances apoptosis induction by platinum complexes in cisplatin-resistant tumor cells.
Cisplatin is one of the most widely used antitumor drugs. However, as all the anticancer drugs currently used in clinic, cisplatin shows the phenomenon of drug resistance (intrinsic or acquired) against a wide variety of tumors. Poly (ADP-ribose) polymerase-1 is an enzyme involved in DNA repair and apoptotic cell death, which may be inhibited to increase cisplatin chemosensitivity of tumor cells so that cisplatin resistance may be circumvented. In the present study we report that PARP-1 inhibitor 3-aminobenzamide (3-AB) increases the cytotoxic activity of the platinum compounds cisplatin, trans-[PtCl(2)(4-picoline)(piperazine)] and transplatin against CH1cisR cisplatin-resistant ovarian tumor cells. In fact, a concentration of 3-AB of 1 mM not only increases the cytotoxic activity of these platinum complexes but also switches the mode of cell death from necrosis to apoptosis. Altogether, these data suggest that pharmacological modulation of PARP-1 by inhibitors may be a suitable strategy to fight against tumor resistance to platinum drugs.
Nguewa
Paul A
PA
Departamento de Parasitología, Facultad de Farmacia, Universidad de La Laguna, Tenerife, Spain.
Fuertes
Miguel A
MA
Cepeda
Victoria
V
Alonso
Carlos
C
Quevedo
Celia
C
Soto
Manuel
M
Pérez
José M
JM
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001549:Benzamides / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D009944:Organoplatinum Compounds; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C025160:3-aminobenzamide; D011065:Poly(ADP-ribose) Polymerases; D002945:Cisplatin