Terpenic subfraction of Pterodon pubescens induces apoptosis of K562 leukemic cells by modulating gene expression

Monica Farah Pereira 1 Thiago Martino 1 Sergio Ranto Dalmau 1 Rodolpho Mattos Albano 1 Jean-Pierre Férézou 2 Sonia Soares Costa 3 Marsen Garcia Pinto Coelho 1 Katia Costa Carvalho Sabino 1, *
* Corresponding author
1 Departamento de Bioquímica
2 DCSO - Laboratoire de synthèse organique
3 Núcleo de Pesquisa em Produtos Naturais
Abstract : Deregulation of cell proliferation and apoptosis is linked to malignant cell development. Leukemia is the most frequent cancer in children, and plants are important sources for new potential anti-cancer agents. Although anti-tumoral effects have been shown for Pterodon pubescens extracts, the mechanisms are still obscure. This study describes in Pterodon pubescens a furane diterpene only reported in Pterodon polygalaeflorus, the methyl-6 alpha-acetoxy-7 beta-hydroxyvouacapan-17 beta-oate, indicated by HRMS and (13)C-NMR analysis, and demonstrates some mechanisms of the anti-leukemia action of its terpene subfraction SF5. SF5 induced cytotoxic and anti-proliferative effects on K562 cells. Increased sub-G1 nuclei and Annexin V(+)-FITC cells confirmed apoptosis of leukemic cells by treatment of these cells with SF5. Down-regulation of DNMT1 gene transcription and over-expression of Apaf-1 mRNA suggested that SF5 may be inducing apoptosis of K562 cells by epigenetic up-regulation of pro-apoptotic proteins involved in the mitochondrial intrinsic pathway.
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Monica Farah Pereira, Thiago Martino, Sergio Ranto Dalmau, Rodolpho Mattos Albano, Jean-Pierre Férézou, et al.. Terpenic subfraction of Pterodon pubescens induces apoptosis of K562 leukemic cells by modulating gene expression. Oncology Reports, Spandidos Publications, 2011, 25 (1), pp.215-221. ⟨10.3892/or_00001063⟩. ⟨hal-00951234⟩

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