Departamento de Bioquímica, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Oncol Rep. 2011 Jan;25(1):215-21.
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.
细胞增殖和凋亡的失调与恶性细胞的发展有关。白血病是儿童中最常见的癌症，而植物是新的潜在抗癌药物的重要来源。尽管已经证明了 Pterodon pubescens 提取物具有抗肿瘤作用，但作用机制仍不清楚。本研究在 Pterodon pubescens 中描述了一种呋喃二萜，仅在 Pterodon polygalaeflorus 中报道过，即甲基-6α-乙酰氧基-7β-羟基沃卡潘-17β-酯，通过 HRMS 和 13C-NMR 分析进行了指示，并证明了其萜类亚组分 SF5 的抗白血病作用的一些机制。SF5 诱导 K562 细胞的细胞毒性和抗增殖作用。通过用 SF5 处理这些细胞，增加的亚 G1 核和 Annexin V+-FITC 细胞证实了白血病细胞的凋亡。DNMT1 基因转录的下调和 Apaf-1 mRNA 的过表达表明，SF5 可能通过参与线粒体内在途径的促凋亡蛋白的表观遗传上调诱导 K562 细胞凋亡。
