Enhanced effectiveness of last generation antiblastic compounds vs. cisplatin on malignant pleural mesothelioma cell lines.
The purpose of this study was to examine the antiproliferative potentialities of a pool of new generation compounds (Paclitaxel, Docetaxel, Gemcitabine, Topotecan, SN-38) together with fenretinide, a synthetic derivative of retinoic acid, in comparison with the current first choice treatment cisplatin molecule, on a pool of human malignant pleural mesothelioma cell lines derived from either bioptic and pleural effusions samples. To evaluate the chemosensitivity features of malignant mesothelioma cells in vitro, we resorted to a rapid and reproducible colorimetric assay, a useful widely recognized tool for preclinical drug screening. In addition, by DNA content analysis and cellular morphologic assessment, we focused on the apoptosis as a potential mechanism of drug activity. The main results clearly indicate that, in all the models of malignant mesothelioma we handled in vitro, each tested antineoplastic agent is more powerful than cisplatin in inhibiting cell proliferation. Moreover, on experimental evidences basis, we can assume that the cytotoxic activity of tested compounds could be related, at least partially, to the drug-induced programmed cell death. This experimental study gives substance to the expected pharmacologic worth of the second generation antineoplastic drugs even if, in order to afford the most satisfactory biopharmacological approach, allowing to bypass the refractoriness to chemotherapy of this highly lethal tumour, further investigations at preclinical level are required.
de Cupis
Alessandra
A
Department of Preclinical Oncology, Laboratory of Pharmacology, Istituto Nazionale per la Ricerca sul Cancro, Largo Rosanna Benzi, 10-16132 Genoa, Italy.
Semino
Claudia
C
Pirani
Paolo
P
Loprevite
Maura
M
Ardizzoni
Andrea
A
Favoni
Roberto E
RE
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002945:Cisplatin / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077143:Docetaxel; D004354:Drug Screening Assays, Antitumor; D017313:Fenretinide / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D000077146:Irinotecan; D008654:Mesothelioma / Q000188:drug therapy*; D017239:Paclitaxel / Q000494:pharmacology; D043823:Taxoids / Q000494:pharmacology; D019772:Topotecan / Q000494:pharmacology; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D017313:Fenretinide; D000077146:Irinotecan; D019772:Topotecan; D017239:Paclitaxel; D002945:Cisplatin; D002166:Camptothecin; D000093542:Gemcitabine