Cisplatin in combination with Phenethyl Isothiocyanate (PEITC), a potential new therapeutic strategy for malignant pleural mesothelioma
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Iza Denis1,2,3, Laurent Cellerin1,2,3,4, Marc Gregoire1,2,3 and Christophe Blanquart1,2,3
1 Inserm, UMR892, Nantes, F-44000, France
2 CNRS, UMR6299, Nantes, F-44000, France
3 Université Nantes, Nantes, F-44000, France
4 Service d’Oncologie Médicale Thoracique et Digestive, Hôpital Laënnec, CHU de Nantes, France
Christophe Blanquart, email:
Keywords: malignant mesothelioma, cisplatin, isothyocyanate, reactive oxygen species, combination treatment
Received: September 24, 2014 Accepted: October 18, 2014 Published: October 18, 2014
Malignant pleural mesothelioma (MPM) is a very aggressive form of cancer with a poor diagnosis and prognosis. The first line treatment for MPM is a combination of cisplatin and Pemetrexed, which displayed limited efficacy and severe side effects. The naturally occurring compound phenethyl isothiocyanate (PEITC) previously showed interesting anti-tumor properties on several cancer cell lines. We thus aim at evaluating PEITC used alone or in combination with cisplatin in order to improve MPM treatment.
Nine MPM cell lines and primary mesothelial cells (PMC), co-cultured or not with M2 macrophages present in MPM microenvironment, were used to assess PEITC and cisplatin anti-tumor properties. Compounds were used alone or in combination.
Both PEITC and cisplatin were cytotoxic on MPM cells in a dose dependent manner. We herein showed that PEITC-induced cytotoxicity was due to the generation of reactive oxygen species. Moreover, we showed that cisplatin-PEITC combination allowed the potentialization of both compounds’ cytotoxic effects and prevented the emergence of resistant MPM cells. Interestingly, PMC were not sensitive to the combination. Finally, we showed that M2 macrophages did not alter the anti-tumor properties of the combination. Cisplatin-PEITC combination thus represents a promising strategy to induce a selective toxicity towards malignant cells.
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