Cisplatin and oxaliplatin cytotoxic effects in sensitive and cisplatin-resistant human cervical tumor cells: time and mode of application dependency.
BACKGROUND
Time-dependence of cisplatin (CDDP) and oxaliplatin (L-OHP) cytotoxic effects in A431 and A431/Pt cells (sensitive and CDDP-resistant human cervical tumor cells) were investigated.


METHODS
The drug application modes were pulse (12.5, 25 or 50 microM up to 72 h) and pulse-plus-chase (50 microM for 2, 4 or 6 h, followed by washing and 72 h-incubation in drug-free medium).


RESULTS
In the A431 cells, the pulse drug application showed time-effect curves with two plateaux; the inhibitory activity of CDDP was higher than that of L-OHP. The same growth-inhibition fraction was reached by L-OHP in a longer time than CDDP. In the A431/Pt cells, the curve shapes for both drugs were similar in both application modes and had the same general characteristics, noted in the parental cell line. CDDP appeared less active than L-OHP.


CONCLUSIONS
Different cytotoxicity curves of Pt-drugs could be dictated by the presence of the bulky diaminocyclohexane (DACH) ligand, affecting the kinetics of Pt-DNA binding; mismatch repair (MSH2) protein is involved in the resistance.
Department of Pharmacology and Anesthesiology, University of Padova, Largo Meneghetti, 2, I-35131 Padova, Italy.
Laura
L
Martelli
Eugenio
E
Ragazzi
Francesco
F
Di Mario
Marino
M
Basato
Mario
M
Martelli
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000077150:Oxaliplatin; D013329:Structure-Activity Relationship; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002945:Cisplatin