Disulfiram suppresses invasive ability of osteosarcoma cells via the inhibition of MMP-2 and MMP-9 expression.
Cancer cells, characterized by local invasion and distant metastasis, are very much dependent on the extracellular matrix. The expression of matrix metalloproteinases (MMPs) has been implicated in the invasion and metastasis of cancer cells. In this study, we reported the effects of disulfiram, a clinically used anti-alcoholism drug, on tumor invasion suppression, as well as its effects on the activity of MMP-2 and MMP-9 in human osteosarcoma cells (U2OS). Disulfiram has been used for alcohol aversion therapy. However, recent reports have shown that disulfiram may have potential in the treatment of human cancers. Herewith, we showed that the anti-tumor effects of disulfiram, in an invasion assay using U2OS cells and that disulfiram has a type IV collagenase inhibitory activity that inhibits expression of genes and proteins responsible for both cell and non-cell mediated invasion on pathways. In conclusion, disulfiram inhibited expression of MMP-2 and MMP-9 and it regulated the invasion of human osteosarcoma cells. These observations raise the possibility of disulfiram being used clinical for the inhibition of cancer invasion.
Cho
Hyun-Ji
HJ
Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Korea.
Lee
Tae-Sung
TS
Park
Jae-Bok
JB
Park
Kwan-Kyu
KK
Choe
Jung-Yoon
JY
Sin
Doo-Il
DI
Park
Yoon-Yub
YY
Moon
Yong-Suk
YS
Lee
Kwang-Gill
KG
Yeo
Joo-Hong
JH
Han
Sang-Mi
SM
Cho
Young-Su
YS
Choi
Myeong-Rak
MR
Park
Nam-Gyu
NG
Lee
Yun-Sik
YS
Chang
Young-Chae
YC
D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D004221:Disulfiram / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D061965:Matrix Metalloproteinase Inhibitors; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D012516:Osteosarcoma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000187:drug effects
D000970:Antineoplastic Agents; D017931:DNA Primers; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D004221:Disulfiram