The Nrf2 transcription factor is a positive regulator of myeloid differentiation of acute myeloid leukemia cells.

摘要: 1α,25-dihydroxyvitamin D3 (1,25D) is a powerful differentiation agent, which has potential for treatment of acute myeloid leukemia (AML), but induces severe hypercalcemia at pharmacologically active doses. We have previously shown that carnosic acid (CA), the polyphenolic antioxidant from rosemary plant, markedly potentiates induced by low concentrations 1,25D in human AML cell lines. Here, we demonstrated similar enhanced responses to 1,25D/CA combination primary leukemic cells derived patients with AML, and determined role Nrf2/antioxidant response element (Nrf2/ARE) pathway these effects using U937 monoblastic as model. CA strongly transactivated ARE-luciferase reporter gene, ARE-responsive genes, NADP(H)-quinone oxidoreductase γ-glutamylcysteine synthetase heavy subunit, elevated cellular glutathione levels. Interestingly, potentiated on activities. Stable tra...