Department of Pharmacognosy and Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, Mississippi 38677, United States.
J Nat Prod. 2010 Nov 29;73(11):1868-72. doi: 10.1021/np100501n. Epub 2010 Oct 7.
The mammea-type coumarin mammea E/BB (1) was found to inhibit both hypoxia-induced and iron chelator-induced hypoxia-inducible factor-1 (HIF-1) activation in human breast tumor T47D cells with IC(50) values of 0.96 and 0.89 μM, respectively. Compound 1 suppressed the hypoxic induction of secreted VEGF protein (T47D cells) and inhibited cell viability/proliferation in four human tumor cell lines. Compound 1 (at 5 and 20 μM) inhibited human breast tumor MDA-MB-231 cell migration. While the mechanisms that underlie their biological activities have remained unknown, prenylated mammea coumarins have been shown to be cytotoxic to human tumor cells, suppress tumor growth in animal models, and display a wide variety of antimicrobial effects. Mechanistic studies revealed that 1 appears to exert an assemblage of cellular effects by functioning as an anionic protonophore that potently uncouples mitochondrial electron transport and disrupts mitochondrial signaling in human tumor cell lines.
Mammea 型香豆素 mammea E/BB（1）被发现能够抑制人乳腺癌 T47D 细胞中缺氧诱导和铁螯合剂诱导的缺氧诱导因子-1（HIF-1）的激活，其 IC50 值分别为 0.96 和 0.89 μM。化合物 1 抑制了 VEGF 蛋白（T47D 细胞）的缺氧诱导，并抑制了四种人肿瘤细胞系的细胞活力/增殖。化合物 1（在 5 和 20 μM 时）抑制了人乳腺癌 MDA-MB-231 细胞的迁移。虽然其生物活性的机制尚不清楚，但已证明被取代的 mammea 香豆素对人肿瘤细胞具有细胞毒性，能够抑制动物模型中的肿瘤生长，并具有广泛的抗菌作用。机制研究表明，1 通过作为阴离子质子载体发挥作用，强烈解偶联线粒体电子传递并破坏人肿瘤细胞系中的线粒体信号，从而发挥一系列细胞作用。
