[Pt(O,O′-acac)(γ-acac)(DMS)] inhibits malignant pleural mesothelioma cells in vitro and in vivo

The aim of this study was to compare antitumor activity of [Pt(O,O’-acac)(γ-acac)(DMS)] in epithelioid and sarcomatoid type of MPM. Thus, we employed the human cell line of epithelioid derivation ZL55, and the sarcomatoid cell line ZL34 in vitro and SCID mice. In epithelioid cells, [Pt(O,O’-acac)(γ-acac)(DMS)] was approximately 12-fold more cytotoxic than cisplatin after 24 h of incubation (IC50 were 3.9±0.11 μM for [Pt(O,O’-acac)(γ-acac)(DMS)] and 46.8±0.6 μM for cisplatin, n=6). Similarly, in sarcomatoid cells cisplatin was significantly less cytotoxic than [Pt(O,O’-acac)(γ-acac)(DMS)] (IC50 48.7±1.7 μM and ND n=4, for [Pt(O,O’-acac)(γ-acac)(DMS) and cisplatin, respectively). In addition, we employed a preclinical model based on the subcutaneous injection of ZL55 and ZL34 malignant pleural mesotelioma cell lines in SCID mice. Remarkably, [Pt(O,O’-acac)(γ-acac)(DMS)] stands out for higher anticancer activity than cisplatin toward both the murine tumor models examined, inducing up to 50% inhibition of tumor growth. Mice inoculated with MPM cells showed a statistically significant reduction of tumor volume at every time point in the [Pt(O,O’-acac)(γ-acac)(DMS)] groups compared with both not treated and cisplatin-treated mice (p < 0.05). In summary, our findings show that [Pt(O,O’-acac)(γ-acac)(DMS)] seems to be more potent than cisplatin in MPM, thus providing a solid starting point for its validation as a suitable candidate for further pharmacological testing.