Effect of sulforaphane on aquaporin-8 in a leukemic cell line

Cancer cells are characterized by an increase in spatially localized reactive oxygen species (ROS) production and by an altered redox environment compared to normal cells. Consequently, signalling pathways that promote cell proliferation, survival, angiogenesis and metastasis are hyper-activated. In particular, hydrogen peroxide (H2O2) derived from NOX family is involved in various redox signal transduction pathways and the aquaporin 8 (AQP8) has been identified as a H2O2 transport facilitator across the plasma membrane. Recent evidence demonstrated that many tumor cell types express elevated level of aquaporin isoforms and highlighted a positive correlation between histological tumor grade and the AQP expression. Sulforaphane (SFN), an isothiocyanate compound present in abundance in cruciferous vegetables, has been found to induce therapeutic effects against a wide array of malignancies in both experimental and epidemiological studies . Therefore, this study aimed at the evaluation of the potential effect of SFN on the modulation of AQP8, NOX2 and p-VEGFR-2 expression in B1647 cell line, a model of acute myeloid leukemia. In fact, we previously demonstrated that AQP8 funnels NOX-derived H2O2, triggered by endogenously generated VEGF, which, in turn, provokes VEGFR-2 phosphorylation and the consequent modulation of many cellular activities, resulting in cell survival and proliferation. As peroxiredoxin (Prx1) represents a member of the so called thiol-based antioxidant system that acts as redox switches to modulate redox signalling pathways, the effect of SFN on Prx1 expression was also evaluated. Unravelling the role of AQP8 in cancer redox signalling, and the effect exerted by SFN on its modulation, can offer new potential target for anti-cancer therapy, suggesting the importance of dietary co-treatment.