Bezafibrate as differentiating factor of human myeloid leukemia cells

Bezafibrate belongs to the class of fibric acid derivatives usually used as antihyperlipidemia agents. From the biochemical point of view, these drugs show intriguing properties which leads one to think they may promote a dif ferentiation process in tumour cells. This new pharmacological activity of fibrates could partially depend on the induction of an oxidative stress. To test this hypothesis, the effect of bezafibrate, as well as of clofibric a cid and gemfibrozil, on growth, functional and cytochemical characteristics of human leukaemia-derived cell lines HL-60, U-937 and K-562 has been stud ied in some details. The results show that bezafibrate, gemfibrozil and clo fibric acid, do induce differentiation in human myeloid leukaemia cell line s as indicated by several differentiation markers, Moreover fibrates, in do se dependent manner, significantly alter the cell cycle distributions, main ly leading to G(0)/G(1) phase increment and G(2)/M phase reduction. The dif ferentiating activity of fibrates could have significant implications both for the pharmacotoxicological profile of this class of compounds and for th e pathophysiology of neoplastic disease.