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Inhibition of Protein Tyrosine Kinase Activity and Induction of Apoptosis in Epithelial Cells by Oxindole Alkaloids of Uncaria tomentosa (Willd.) D. C

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Author(s): John P. Berry | Maria Laux | Eloy Rodriguez

Journal: Journal of Medical Sciences
ISSN 1682-4474

Volume: 2;
Issue: 3;
Start page: 110;
Date: 2002;
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Keywords: Uncaria tomentosa | oxindole alkaloid | protein tyrpsine kinase | cytotoxic

ABSTRACT
Root bark of Uncaria tomentosa (Willd.) D. C. is used for a variety of therapeutic purposes, including reported efficacy as both an immunostimulant and anticancer therapy. The oxindole alkaloids (OAs) of U. tomentosa were investigated for cytotoxicity toward epithelial cells, specifically focusing on lines derived from breast (MB-MDA-231, MB-MDA-468, BT-20 and SKBR-3) and skin (A431) carcinomas, as well as a non-cancer line (Cos). Alkaloid extracts were shown to be minimally cytotoxic at concentrations as low as 27M, with an IC50 in the range of 0.9 to 1.7 mM, depending on the cell line tested. Microscopic evaluation of cells treated with marginally cytotoxic levels of OAs, and stained with fluorescent indicators, propidium iodide and Hoechst 33342, specifically demonstrate the induction of apoptosis, rather than necrosis. Evaluation of protein tyrosine kinase (PTK) activity in treated cells further demonstrated that minimally cytotoxic concentrations of the OAs inhibited tyrosine phosphorylation of endogenous proteins in MB-MDA-231 cells, when compared to controls. Given the recognized role of protein tyrosine kinases in the coordination of cell proliferation, in this research, propose that inhibition of PTK activity by the OAs contributes to the apoptotic cell-death, and perhaps other biological activities associated with these compounds.

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Tangokurs Rapperswil-Jona

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