Natural compounds as modulators of transduction pathways in tumor cells / Copostos naturais como moduladores de vias de transdução de sinal em celulas tumorais

AUTOR(ES)

Roberta Regina Ruela de Sousa

DATA DE PUBLICAÇÃO

2008

RESUMO

The search for compounds that specifically act on tumors, with low side effects, is a great aim in the studies related to cancer treatment. Many natural compounds isolated from plants have presented promising results as modulating agents of the signal transduction pathways in several types of tumors. Flavonoids, polyphenolic compounds largely distributed in foods such as fruits, teas and wines, have been greatly focused due to their chemopreventive and chemotherapeutic effects. In the last years, many studies about the action of terpenes in diseases have been done, due to their antiinflamatory, antimicrobial, gastroprotective and antitumoral properties. However, few molecular studies have been developed to understand the mechanism of cell death induction by these compounds. The aim of this work was to define the molecular action of apigenin, fisetin and ferruginol on the signal transduction pathways involved in the leukemic and prostate cancer cells proliferation and death. All the three compounds studied provoked the cell death by apoptosis. Leukemic cells treated with fisetin presented an increase of NF?B expression and protein phosphorylation levels and activation of p38 MAPK. Apigenin showed to be a strong inhibitor of kinases involved with cellular proliferation, such as, PI3K, AKT, Src, MAPK and additionally to induce apoptosis via the intrinsic pathway. Ferruginol was able to inhibit and/or to negatively regulate PI3K, STAT3 and 5, protein tyrosine phosphatases and protein kinases involved in the regulation of the cell cycle. In reducing environment, the cytotoxic effect of ferruginol was drastically impeded, which indicates that the anti-tumoral activity of ferruginol might be related to redox status modulation. The present work showed that the natural compounds fisetin, apigenin and ferruginol presented great potential as chemotherapeutic agents

ASSUNTO(S)

flavonoids sinalização celular apoptosis flavonoides ferruginol natural compound terpenes compostos naturais apoptose cell-signalling

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