Butyric acid increases invasiveness of HL-60 leukemia cells: role of reactive oxygen species.
Butyric acid (BA) induces differentiation of human leukemia, including HL-60 cells. By using a fluorescent probe, we showed that reactive oxygen species (ROS) were generated in BA-treated cells. BA-induced differentiation was accompanied with an increased secretion of pro-matrix metalloproteinase (MMP)-9. Both phenomena were inhibited by antioxidants. Tissue inhibitors of MMP (TIMP)-1 and -2 secretion were increased by BA, but differently affected by antioxidants. By contrast, BA did not affect MMP-9 mRNA, and decreased TIMP-1 and TIMP-2 mRNA levels. In addition, migratory and invasive properties of HL-60 cells were enhanced by BA, but differently affected by antioxidants. Altogether, these results indicate that ROS are messengers of BA-induced differentiation and increased invasiveness.
Richard
Doriane
D
Unité MéDIAN, CNRS FRE-2141, Université de Reims-Champagne Ardenne, Faculté de Pharmacie, 51 rue Cognacq-Jay, F-51096 Cedex, Reims, France.
Hollender
Patrick
P
Chénais
Benoît
B
D000975:Antioxidants / Q000494:pharmacology; D020148:Butyric Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D009361:Neoplasm Invasiveness; D012334:RNA, Neoplasm / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis
D000975:Antioxidants; D012334:RNA, Neoplasm; D017382:Reactive Oxygen Species; D019714:Tissue Inhibitor of Metalloproteinases; D020148:Butyric Acid; D020780:Matrix Metalloproteinase 9