Antiproliferative effects of mitraphylline, a pentacyclic oxindole alkaloid of Uncaria tomentosa on human glioma and neuroblastoma cell lines

García Prado, E.; García Gimenez, M.D.; De la Puerta Vázquez, R.; Espartero Sánchez, J.L.; Sáenz Rodríguez, M.T.

doi:10.1016/j.phymed.2006.12.023

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Volume 14, Issue 4 , Pages 280-284, 10 April 2007

Antiproliferative effects of mitraphylline, a pentacyclic oxindole alkaloid of Uncaria tomentosa on human glioma and neuroblastoma cell lines

E. García Prado
- Department of Pharmacology, Faculty of Pharmacy, University of Seville, c/ Profesor García González n. 2, 41012 Seville, Spain
M.D. García Gimenez
- Department of Pharmacology, Faculty of Pharmacy, University of Seville, c/ Profesor García González n. 2, 41012 Seville, Spain
R. De la Puerta Vázquez
- Department of Pharmacology, Faculty of Pharmacy, University of Seville, c/ Profesor García González n. 2, 41012 Seville, Spain
J.L. Espartero Sánchez
- Department of Organic and Pharmaceutical Chemistry, Faculty of Pharmacy, University of Seville, Seville, Spain
M.T. Sáenz Rodríguez
- Department of Pharmacology, Faculty of Pharmacy, University of Seville, c/ Profesor García González n. 2, 41012 Seville, Spain
- Corresponding author.

Received 1 March 2006; accepted 7 December 2006.

Abstract

Uncaria tomentosa inner bark extract is a popular plant remedy used in folk medicine to treat tumor and inflammatory processes. In this study, the anti-tumoral effects of its pentacyclic alkaloid mitraphylline were investigated. Furthermore, its growth-inhibitory and cytotoxic effects on glioma GAMG and neuroblastoma SKN-BE(2) cell lines were studied using cyclophosphamide and vincristine as controls. A colter counter was used to determine viable cell numbers, followed by application of the tetrazolium compound [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)2-(4-sulfophenyl)-2H-tetrazolium], inner salt, colorimetric method to evaluate cell viability in this cytotoxicity assay. Micromolar concentrations of mitraphylline (from 5 to 40μM) inhibited the growth of both cell lines. It inhibited the growth of the two cell lines studied in a dose-dependent manner. The IC₅₀ values were 12.3μM (30h) for SKN-BE(2) and 20μM (48h) for GAMG, respectively. This action suggests that mitraphylline is a new and promising agent in the treatment of human neuroblastoma and glioma.