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Type: Artigo de periódico
Title: Ferruginol Suppresses Survival Signaling Pathways In Androgen-independent Human Prostate Cancer Cells.
Author: Bispo de Jesus, Marcelo
Zambuzzi, Willian Fernando
Ruela de Sousa, Roberta Regina
Areche, Carlos
Santos de Souza, Ana Carolina
Aoyama, Hiroshi
Schmeda-Hirschmann, Guillermo
Rodríguez, Jaime A
Monteiro de Souza Brito, Alba Regina
Peppelenbosch, Maikel P
den Hertog, Jeroen
de Paula, Eneida
Ferreira, Carmen Veríssima
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.
Subject: Androgens
Antineoplastic Agents
Apoptosis Inducing Factor
Cell Cycle
Cell Line, Tumor
Cell Proliferation
Cell Survival
Diterpenes, Abietane
I-kappa B Kinase
Prostatic Neoplasms
Protein Tyrosine Phosphatases
Proto-oncogene Proteins
Stat Transcription Factors
Signal Transduction
Citation: Biochimie. v. 90, n. 6, p. 843-54, 2008-Jun.
Rights: fechado
Identifier DOI: 10.1016/j.biochi.2008.01.011
Date Issue: 2008
Appears in Collections:Unicamp - Artigos e Outros Documentos

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