Azelaic acid decreases the fibrinolytic potential of cultured human melanoma cells in vitro.
Azelaic acid (AZA) has been used successfully in the treatment of lentigo maligna melanoma. Since it is generally accepted that the fibrinolytic potential of tumour cells is related to their malignant phenotype, it was the aim of this study to investigate the effect of AZA on the fibrinolytic potential of three different human melanoma cell lines (Bowes, GUBSB and MJZJ). Melanoma cells were incubated with AZA in doses ranging from 10(-2) M to 4 x 10(-2) M for 5, 8 and 24 h. The expression of tissue-type plasminogen activator (t-PA), urokinase-type PA (u-PA) and PA inhibitor-1 (PAI-1) in such treated cells was investigated by specific ELISAs on the protein level and by Northern blotting on the mRNA level. AZA caused a time and dose dependent decrease in the fibrinolytic potential of all three cell lines investigated by decreasing t-PA antigen in Bowes, by decreasing u-PA antigen in GUBSB and by increasing PAI-1 antigen in MJZJ cells, respectively. There was no significant difference between the viability of cells in control cultures and those treated with AZA. The effect of AZA on specific mRNA for t-PA in Bowes cells, u-PA in GUBSB and PAI-1 in MJZJ was consistent with its effect on the secretion of these fibrinolytic proteins by the respective cells. The results show that AZA decreases the fibrinolytic potential of the three human melanoma cell lines in vitro. This decrease may be operative in the mechanism by which AZA has been shown to affect malignant melanoma in vivo.
Addo-Boadu
K
K
Department of Medicine and Physiology, University of Vienna, Austria.
Wojta
J
J
Christ
G
G
Hufnagl
P
P
Pehamberger
H
H
Binder
B R
BR
D000970:Antineoplastic Agents / Q000494:pharmacology*; D003998:Dicarboxylic Acids / Q000494:pharmacology*; D005342:Fibrinolysis / Q000187:drug effects*; D015870:Gene Expression; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
D000970:Antineoplastic Agents; D003998:Dicarboxylic Acids; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; C010038:azelaic acid