Terpenic subfraction of Pterodon pubescens induces apoptosis of K562 leukemic cells by modulating gene expression.
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-6α-acetoxy-7β-hydroxyvouacapan-17β-oate, indicated by HRMS and 13C-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.
Departamento de Bioquímica, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Monica Farah
MF
Pereira
Thiago
T
Martino
Sergio Ranto
SR
Dalmau
Rodolfo Mattos
RM
Albano
Jean-Pierre
JP
Férézou
Sonia Soares
SS
Costa
Marsen Garcia Pinto
MG
Coelho
Kátia Gosta Carvalho
KG
Sabino
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology; D007887:Fabaceae / Q000737:chemistry*; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000235:genetics*; D010936:Plant Extracts / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; D004224:Diterpenes; D010936:Plant Extracts