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Cho, Hyun-Ji,Lee, Tae-Sung,Park, Jae-Bok,Park, Kwan-Kyu,Choe, Jung-Yoon,Sin, Doo-Il,Park, Yoon-Yub,Moon, Yong-Suk,Lee, Kwang-Gill,Yeo, Joo-Hong,Han, Sang-Mi,Cho, Young-Su,Choi, Myeong-Rak,Park, Nam-Gy Korean Society for Biochemistry and Molecular Biol 2007 Journal of biochemistry and molecular biology Vol.40 No.6
Cancer cells, characterized by local invasion and distant metastasis, are very much dependant 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.
Regulation of insulin response in skeletal muscle cell by caveolin status
Oh, Yoon Sin,Cho, Kyung A.,Ryu, Sung Jin,Khil, Lee-Yong,Jun, Hee-Sook,Yoon, Ji-Won,Park, Sang Chul Wiley Subscription Services, Inc., A Wiley Company 2006 Journal of cellular biochemistry Vol.99 No.3
<P>Recent studies on the role of caveolin-1 in adipocytes showed that caveolin has emerged as an important regulatory element in insulin signaling but little is known on its role in skeletal muscle cells. In this study, we demonstrate for the first time that caveolin-1 plays a crucial role in insulin dependent glucose uptake in skeletal muscle cells. Differentiation of L6 skeletal muscle cells induce the expression of caveolin-1 and caveolin-3 with partial colocalization. However in contrast to adipocytes, phosphorylation of insulin receptor β (IRβ) and Akt/Erk was not affected by the respective downregulation of caveolin-1 or caveolin-3 in the muscle cells. Moreover, the phosphorylation of IRβ was detected not only in the caveolae but also in the non-caveolae fractions of the muscle cells despite the interaction of IRβ with caveolin-1 and caveolin-3. These data implicate the lack of relationship between caveolins and IRβ pathway in the muscle cells, different from the adipocytes. However, glucose uptake was reduced specifically by downregulation of caveolin-1, but not that of caveolin-3. Taken together, these observations suggest that caveolin-1 plays a crucial role in glucose uptake in differentiated muscle cells and that the regulation of caveolin-1 expression may be an important mechanism for insulin sensitivity, implying the role of muscle cells for type 2 diabetes. J. Cell. Biochem. 99: 747–758, 2006. © 2006 Wiley-Liss, Inc.</P>