Abstract
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.
Highlights
Malignant pleural mesothelioma (MPM) is an aggressive neoplasm affecting the mesothelial surfaces of pleural and peritoneal cavities [1] mainly arising from a chronic exposure to and inhalation of asbestos [2]
In order to evaluate the antitumor properties of phenethyl isothiocyanate (PEITC), cell cytotoxic assays were conducted on three MPM cell lines: Meso4, Meso11, Meso152, treated with increasing doses of PEITC alone or in combination with NAC, a powerful antioxidant amino acid
Cell cytotoxicity with PEITC treatment was increased in a dose-dependent manner, and PEITC had a similar potency on all cell lines
Summary
Malignant pleural mesothelioma (MPM) is an aggressive neoplasm affecting the mesothelial surfaces of pleural and peritoneal cavities [1] mainly arising from a chronic exposure to and inhalation of asbestos [2]. Its aggressiveness and critical health care matter mainly arise from its late diagnosis and poor prognosis (less than a year after diagnosis). There are several clinical trials relating this combination to treat MPM [34], that lead to better response compared to cisplatin alone [5]. This improvement remains modest and only half of the patients respond to the combination [6]. It is necessary to find new therapeutic approaches to treat MPM
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