Sulforaphane displays the growth inhibition, cytotoxicity and enhancement of retinoic acid-induced superoxide-generating activity in human monoblastic U937 cells

Sulforaphane [1-isothiocyanato-4-(methyl-sulfinyl)butane] is an isothiocyanate derivative from cruciferous vegetables, with anti-proliferative actions on various cancer and tumor cells. In this paper, we envisaged the effects of sulforaphane on various functions (growth inhibition, cytotoxicity and enhancement of O2--generating activity) of human monoblastic leukemia U937 cells. Sulforaphane showed strong cytotoxicity, resulting in inhibition of proliferation in a dose-dependent manner. In addition, cell differentiation induced by 1 μM all-trans retionic acid (RA) remarkably caused the enhanced resistance against cytotoxicity of sulforaphane. Moreover, the RA-induced O2--generating activity was also enhanced by sulforaphane in a dose dependent manner. When U937 cells were cultured in the presence of 1 μM RA and 2 μM sulforaphane, the O2--generating activity increased more than 2.5-fold compared with that in the absence of the latter. Semiquantitative RT-PCR showed that co-treatment with RA and sulforaphane slightly enhanced transcription of only p47-phox gene among five essential components (p22-phox, gp91-phox, p40-phox, p47-phox and p67-phox) for the O2--generating system in phagocytes. On the other hand, immunoblot analysis revealed that co-treatment with RA and sulforaphane caused accumulation of protein levels of p47-phox (upto ~130%) and p67-phox (upto ~240%) compared with those of the RA-treatment alone. These results indicated that sulforaphane may enhance the RA-induced O2--generating activity in U937 cells via accumulation of p47-phox and p67-phox proteins. These data suggested that sulforaphane may serve as an effective drug for leukemia treatment.