Library Subscription: Guest
Begell Digital Portal Begell Digital Library eBooks Journals References & Proceedings Research Collections
Journal of Environmental Pathology, Toxicology and Oncology
IF: 1.241 5-Year IF: 1.349 SJR: 0.356 SNIP: 0.613 CiteScore™: 1.61

ISSN Print: 0731-8898
ISSN Online: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.v29.i1.80
pages 55-68

Black Tea Polyphenol (Theaflavin) Downregulates MMP-2 in Human Melanoma Cell Line A375 by Involving Multiple Regulatory Molecules

Hrishikesh Sil
Department of Receptor Biology & Tumor Metastasis, Chittaranjan National Cancer, Institute, 37, S P Mukherjee Road, Kolkata - 700 026, West Bengal
Triparna Sen
Department of Receptor Biology & Tumor Metastasis, Chittaranjan National Cancer, Institute, 37, S P Mukherjee Road, Kolkata - 700 026, West Bengal
Shuvojit Moulik
Department of Receptor Biology & Tumor Metastasis, Chittaranjan National Cancer, Institute, 37, S P Mukherjee Road, Kolkata - 700 026, West Bengal
Amitava Chatterjee
Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, 37 S.P. Mukherjee Road, Kolkata-700 026, India

ABSTRACT

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.


Articles with similar content:

Cell Membrane-Associated MT1-MMP-Dependent Activation of Pro-MMP-2 in A375 Melanoma Cells
Journal of Environmental Pathology, Toxicology and Oncology, Vol.24, 2005, issue 1
Amitava Chatterjee, Jayati Chakrabarti, Aparna Mitra, Aniruddha Banerji
The Novel Role of Yin Yang 1 in the Regulation of Epithelial to Mesenchymal Transition in Cancer Via the Dysregulated NF-κB/Snail/YY1/RKIP/PTEN Circuitry
Critical Reviews™ in Oncogenesis, Vol.16, 2011, issue 3-4
Stavroula Baritaki, Benjamin Bonavida
Protective Effect of Solanum muricatum on Tumor Metastasis by Regulating Inflammatory Mediators and Nuclear Factor-Kappa B Subunits
Journal of Environmental Pathology, Toxicology and Oncology, Vol.34, 2015, issue 3
Chandrasekaran Guruvayoorappan, Kittappa Shathish, Kunnathur Murugesan Sakthivel
Yin Yang 1 and raf-1 Kinase Inhibitory Protein Status in Hepatocellular carcinoma: Future Perspectives
Forum on Immunopathological Diseases and Therapeutics, Vol.1, 2010, issue 1-2
Luigi Inguglia, Melchiorre Cervello, Manuela Labbozzetta, Giuseppe Montalto, Rossana Porcasi, Lydia Giannitrapani, Paola Poma, Monica Notarbartolo, Natale D'Alessandro, Ada Maria Florena
Binding of a5 Monoclonal Antibody to Cell Surface a5b1 Integrin Modulates MMP-2 and MMP-7 Activity in B16F10 Me
Journal of Environmental Pathology, Toxicology and Oncology, Vol.22, 2003, issue 3
Amitava Chatterjee, Jayati Chakrabarti, Aparna Mitra