RT Journal Article
ID 5ab2496e2d522b2c
A1 Sil, Hrishikesh
A1 Sen, Triparna
A1 Moulik, Shuvojit
A1 Chatterjee, Amitava
T1 Black Tea Polyphenol (Theaflavin) Downregulates MMP-2 in Human Melanoma Cell Line A375 by Involving Multiple Regulatory Molecules
JF Journal of Environmental Pathology, Toxicology and Oncology
JO JEP(T)
YR 2010
FD 2010-04-23
VO 29
IS 1
SP 55
OP 68
K1 black tea polyphenol
K1 theaflavin
K1 MMP-2
K1 MT1-MMP
K1 TIMP-2
K1 integrins
K1 FAK
K1 signaling
AB The tumor-inhibiting property of black tea polyphenol, theaflavin, is well documented. Matrix metalloproteinases (MMPs) play a pivotal role in tumor invasion through degradation of extracellular matrix (ECM). In the present study, we observed the effect of theaflavin on MMP-2, which is upregulated in most tumor types, and its regulatory molecules, in human melanoma cell line, A375. The treatment of theaflavin downregulated the gelatinolytic activity, mRNA and protein expression of MMP-2. It reduced the mRNA and protein expression of membrane type-1 MMP (MT1-MMP) and induced mRNA and protein expression of tissue inhibitor of MMP-2 (TIMP-2), suggesting theaflavin's inhibitory effect on MMP-2 activation. Theaflavin reduced the binding of A375 cell to ECM ligands demonstrating that theaflavin treatment hinders cell-ECM adhesion, cell motility, and integrin-mediated MMP-2 activation. Theaflavin treatment inhibited the protein expression FAK EGFR and ERK, suggesting that, theaflavin treatment downregulates the molecules participating in MMP-2 secretion and regulation. The downregulation of NFχB suggests downregulation of MMP-2 transactivation. Theaflavin also reduced the tumor volume in syngenic black mice. Thus, we report that theaflavin causes an inhibition of the expression and activity of pro-MMP-2 by a process involving multiple regulatory molecules in human melanoma cells, A375.
PB Begell House
LK https://www.dl.begellhouse.com/journals/0ff459a57a4c08d0,265fcbc773531109,5ab2496e2d522b2c.html