Cytotoxicity of paclitaxel in combination with cisplatin and a new Pt-mercaptopyridine complex.
In vitro synergy has been reported for exposure to paclitaxel prior to cis-platin (cis-DDP), whereas the reverse sequence resulted in antagonism. There is no clear evidence for an intracellular origin of the schedule-dependent interaction, but several hypotheses have been proposed, such as effects at the level of DNA crosslinks, or binding to tubulin sites. The purpose of this study was to evaluate the cytotoxicity of these two drugs as single agents, in combination and in sequence, against a human colon adenocarcinoma cell line (LoVo). Moreover, we considered the new Pt-mercaptopyridine complex C/2, was like cis-platin in being able to alter DNA conformation. We have therefore studied the cytotoxic effects after single agent exposure, concomitant exposure (paclitaxel + cis-platin and paclitaxel + C/2) and sequential drugs exposure (paclitaxel-->cis-platin and cis-platin-->paclitaxel or paclitaxel-->C/2 and C/2-->paclitaxel). Our results demonstrate that the most cytotoxic effect is induced by paclitaxel and C/2 exposure both in the case of concomitant cell treatment and sequential exposure paclitaxel-->C/2.
Ragazzi
E
E
Department of Pharmacology and Anaesthesiology, University of Padua, Largo E. Meneghetti, 2, 35131 Padova, Italy.
D'Ancona
S
S
Berti
E
E
Carrara
M
M
D000230:Adenocarcinoma / Q000188:drug therapy; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D006801:Humans; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology*; D011725:Pyridines / Q000008:administration & dosage; D014407:Tumor Cells, Cultured
D009944:Organoplatinum Compounds; D011725:Pyridines; D017239:Paclitaxel; D002945:Cisplatin