Журнал канцерогенеза и мутагенеза

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Pharmacological Induction of Heme Oxygenase-1 Reduces KB Cell Viability:Role of Carbon Monoxide

Russo Alessandra, Berretta Massimiliano, Cardile Venera, Lombardo Laura, Vanella Luca, Troncoso Nicolas, Garbarino Juan, Ignazio Barbagallo and Li Volti Giovanni

Heme oxygenase-1 (Hmox1) catalyzes the rate-limiting step in heme degradation, releasing iron, carbon monoxide (CO), and biliverdin. The aim of the present study was to investigate Hmox1 as a possible mechanism underlying propolis cytotoxic effects in KB cells. Cells were cultured for 24, 48 and 72 hours and treated with propolis or SnCl2, known inducers of Hmox1 protein expression and activity. Propolis and SnCl2 treatments decreased cell viability and induced Hmox1 expression. Furthermore, propolis increased LDH release and decreased dramatically reactive oxygen species (ROS) formation. Toxic effects of both propolis and SnCl2 were reversed by tin-mesoporphirin (SnMP), a Hmox activity inhibitor. No significant effect was observed on p21 expression following propolis treatment. By contrast, SnCl2 decreased ROS formation and increased p21 expression but did not affect LDH release. These results were further confirmed by the use of CO releasing molecule (tricarbonyldichlororuthenium dimer (II)) (CORM-II) treatment (10-40 μM). Our results suggest that propolis mediates KB cell cytotoxicity, in part by Hmox1 induction, and that KB cells are very sensitive to Hmox1 derived CO, a property that may be relevant for oral squamous cell carcinoma therapy.