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Anticancer Res ; 29(8): 3233-8, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19661340

RESUMO

Ascorbate has dose-dependent inverse effects on cancer cells growth and expression of matrixmetalloproteinases (MMP) and transforming growth factor-beta (TGF-beta), which regulate extracellular matrix (ECM) remodeling. We examined melanoma cell viability and ECM remodeling mechanisms of ascorbate and its modulation by an extract from Polypodium leucotomos (PL) (a fern) via the regulation of apoptosis, heat-shock proteins (HSPs), MMP-1 or tissue inhibitors of matrix metalloproteinase-1 (TIMP-1) that inhibits MMP-1. The dose-dependent regulation of cell viability/proliferation by ascorbate was associated with inverse regulation of apoptosis and stimulation of HSPs at growth-inhibitory concentrations. PL antagonized the stimulation of MMP-1, TGF-beta and HSPs by a growth-inhibitory ascorbate dose and stimulated the expression of TIMP-1, while maintaining growth inhibition. We infer that a combination of ascorbate with PL is beneficial to cancer management via the simultaneous inhibition of cell growth and expression of MMP-1, TGF-beta and HSPs, and furthermore, the stimulation of TIMP-1.


Assuntos
Antioxidantes/farmacologia , Ácido Ascórbico/farmacologia , Proliferação de Células/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Melanoma/tratamento farmacológico , Extratos Vegetais/farmacologia , Polypodium , Protocolos de Quimioterapia Combinada Antineoplásica , Caspase 3/metabolismo , Células Cultivadas , Sinergismo Farmacológico , Ensaio de Imunoadsorção Enzimática , Matriz Extracelular/metabolismo , Proteínas de Choque Térmico/metabolismo , Humanos , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 1 da Matriz/metabolismo , Inibidores de Metaloproteinases de Matriz , Melanoma/metabolismo , Melanoma/patologia , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Células Tumorais Cultivadas
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