Chemical enhancement of cisplatin cytotoxicity in a human ovarian and cervical cancer cell line.
While many advances have been made in the chemotherapy of gynecologic cancers, treatment failures remain a major clinical problem. A growing understanding of the mechanisms of tumor cell resistance to antineoplastic drugs provides a framework for the development of chemotherapy regimens containing agents capable of modulating tumor response. Using a short-term ATP bioluminescence assay we studied the ability of two methylxanthines (caffeine, pentoxifylline) and an inhibitor of ADP-ribosyl transferase (3-aminobenzamide) to enhance cisplatin cytotoxicity in gynecologic cancer cell lines. Our findings of significantly enhanced cisplatin-induced cytotoxicity with two different analysis techniques confirms the effectiveness of these agents. These results may have future clinical significance.
Boike
G M
GM
Division of Gynecologic Oncology, University of Miami, Florida 33101.
Petru
E
E
Sevin
B U
BU
Averette
H E
HE
Chou
T C
TC
Penalver
M
M
Donato
D
D
Schiano
M
M
Hilsenbeck
S G
SG
Perras
J
J
D000255:Adenosine Triphosphate / Q000032:analysis; D001549:Benzamides; D002110:Caffeine / Q000494:pharmacology; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004357:Drug Synergism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010431:Pentoxifylline / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000494:pharmacology; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
D001549:Benzamides; D002110:Caffeine; C025160:3-aminobenzamide; D000255:Adenosine Triphosphate; D011065:Poly(ADP-ribose) Polymerases; D002945:Cisplatin; D010431:Pentoxifylline