Cisplatin and Oxaliplatin Cytotoxic Effects in Sensitive and Cisplatin-resistant Human Cervical Tumor Cells: Time and Mode of Application Dependency
- 1Department of Pharmacology and Anesthesiology, University of Padova, Padova
- 2Department of Clinical Sciences, Section of Gastroenterology, University of Parma, Parma, Italy
- 3Department of Chemical Sciences, University of Padova, Padova
- Correspondence to: Eugenio Ragazzi, MD, Department of Pharmacology and Anesthesiology, University of Padova, Largo Meneghetti, 2, I-35131 Padova, Italy. Tel. +39 0498275775, Fax: +39 0498275093, e-mail: eugenio.ragazzi{at}unipd.it
Abstract
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. Materials and Methods: The drug application modes were pulse (12.5, 25 or 50 μM up to 72 h) and pulse-plus-chase (50 μM for 2, 4 or 6h, 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. Conclusion: 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.
- A431 and A431/Pt human cervical tumor cell lines
- platinum drugs
- prolonged drug incubation
- cytotoxic effect
- Received April 27, 2009.
- Revision received July 20, 2009.
- Accepted August 21, 2009.
- Copyright© 2009 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
