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 differentiation 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 acid and gemfibrozil, on growth, functional and cytochemical characteristics of human leukaemia-derived cell lines HL-60, U-937 and K-562 has been studied in some details. The results show that bezafibrate, gemfibrozil and clofibric acid, do induce differentiation in human myeloid leukaemia cell lines as indicated by several differentiation markers. Moreover fibrates, in dose dependent manner, significantly alter the cell cycle distributions, mainly leading to G0/G1 phase increment and G2/M phase reduction. The differentiating activity of fibrates could have significant implications both for the pharmacotoxicological profile of this class of compounds and for the pathophysiology of neoplastic disease.
Scatena
R
R
Institute of Chemistry and Clinical Chemistry, Catholic University, Rome, Italy. r.scatena@uniserv.ccr.rm.cnr.it
Nocca
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G
Sole
P D
PD
Rumi
C
C
Puggioni
P
P
Remiddi
F
F
Bottoni
P
P
Ficarra
S
S
Giardina
B
B
D000111:Acetylcysteine / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D001629:Bezafibrate / Q000494:pharmacology*; D015415:Biomarkers; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002995:Clofibric Acid / Q000031:analogs & derivatives; D015248:Gemfibrozil / Q000494:pharmacology; D006131:Growth Inhibitors / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D016167:Integrin alphaXbeta2 / Q000096:biosynthesis; D020014:K562 Cells; D007951:Leukemia, Myeloid; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D020298:U937 Cells
D000970:Antineoplastic Agents; D000975:Antioxidants; D015415:Biomarkers; D006131:Growth Inhibitors; D016167:Integrin alphaXbeta2; D018950:Lipopolysaccharide Receptors; D002995:Clofibric Acid; D015248:Gemfibrozil; D000111:Acetylcysteine; D001629:Bezafibrate