Ferruginol suppresses survival signaling pathways in androgen-independent human prostate cancer cells.

M. Bispo de Jesus, W.F. Zambuzzi, R.R. Ruela de Sousa, C. Areche, A.C. Santos de Souza, H. Aoyama, G. Schmeda-Hirschmann, J.A. Rodriguez, A.R. Monteiro de Souza Brito, M.P. Peppelenbosch, J. den Hertog, E. de Paula, C.V. Ferreira

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

Ferruginol, a bioactive compound isolated from a Chilean tree (Podocarpaceae), attracts attention as a consequence of its pharmacological properties, which include anti-fungal, anti-bacterial, cardioprotective, anti-oxidative, anti-plasmodial and anti-ulcerogenic actions. Nevertheless, the molecular basis for these actions remains only partly understood and hence we investigated the effects of ferruginol on androgen-independent human prostate cancer cells (PC3), a known model for solid tumor cells with an exceptional resistance to therapy. The results show that ferruginol induces PC3 cell death via activation of caspases as well as apoptosis-inducing factor (AIF) as confirmed by its translocation into the nucleus. In order to clarify the biochemical mechanism responsible for the anti-tumor activity of ferruginol, we analyzed a set of molecular mediators involved in tumor cell survival, progression and aggressiveness. Ferruginol was able to trigger inhibition/downregulation of Ras/PI3K, STAT 3/5, protein tyrosine phosphatase and protein kinases related to cell cycle regulation. Importantly, the toxic effect of ferruginol was dramatically impeded in a more reducing environment, which indicates that at least in part, the anti-tumoral activity of ferruginol might be related to redox status modulation. This study supports further examination of ferruginol as a potential agent for both the prevention and treatment of prostate cancer.
Original languageEnglish
Pages (from-to)843-854
JournalBiochimie
Volume90
Issue number6
DOIs
Publication statusPublished - 2008

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