Carnosic acid potentiates the antioxidant and prodifferentiation effects of 1 alpha 25-dihydroxyvitamin D-3 in leukemia cells but does not promote elevation of basal levels of intracellular calcium

Differentiation therapy of cancer remains an only partially attained goal. Agents currently under active investigation include derivatives of vitamin D, modeled on its physiological hormone form, 1α,25-dihydroxyvitamin D3 (1,25D3), but the calcemic effects of these compounds preclude their use in the clinic. An approach that may obviate this problem is to combine 1,25D3 or its derivatives with other agents that increase the antineoplastic effects of low, nontoxic concentrations of vitamin D compounds. We have recently used the plant-derived polyphenolic antioxidant, carnosic acid (CA), to demonstrate an increase in the differentiating action of 1,25D3 on human leukemia cells under these conditions (M. Danilenko et al., JNCI, 93: 1224–1233, 2001). We now show that treatment of HL60-G cells with either CA or 1,25D3 alone resulted in a decrease in the intracellular levels of reactive oxygen species.