Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Phytomedicine. 2012 Jan 15;19(2):138-44. doi: 10.1016/j.phymed.2011.07.001. Epub 2011 Sep 7.
Bioactive compounds from the medicinal plant, Eurycoma longifolia Jack have been shown to promote anti-proliferative effects on various cancer cell lines. Here we examined the effects of purified eurycomanone, a quassinoid found in Eurycoma longifolia Jack extract, on the expression of selected genes of the A549 lung cancer cells. Eurycomanone inhibited A549 lung cancer cell proliferation in a dose-dependent manner at concentrations ranging from 5 to 20 μg/ml. The concentration that inhibited 50% of cell growth (GI(50)) was 5.1 μg/ml. The anti-proliferative effects were not fully reversible following the removal of eurycomanone, in which 30% of cell inhibition still remained (p<0.0001, T-test). At 8 μg/ml (GI(70)), eurycomanone suppressed anchorage-independent growth of A549 cells by >25% (p<0.05, T-test, n=8) as determined using soft agar colony formation assay. Cisplatin, a chemotherapy drug used for the treatment of non small cell lung cancer on the other hand, inhibited A549 cells proliferation at concentrations ranging from 0.2 μg/ml to 15 μg/ml with a GI(50) of 0.58 μg/ml. The treatment with eurycomanone reduced the abundance expression of the lung cancer markers, heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1, p53 tumor suppressor protein and other cancer-associated genes including prohibitin (PHB), annexin 1 (ANX1) and endoplasmic reticulum protein 28 (ERp28) but not the house keeping genes. The mRNA expressions of all genes with the exception of PHB were significantly downregulated, 72 h after treatment (p<0.05, T-test, n=9). These findings suggest that eurycomanone at viable therapeutic concentrations of 5-20 μg/ml exhibited significant anti-proliferative and anti-clonogenic cell growth effects on A549 lung cancer cells. The treatment also resulted in suppression of the lung cancer cell tumor markers and several known cancer cell growth-associated genes.
从药用植物长柄铁心木中提取的生物活性化合物已被证明对多种癌细胞系具有抗增殖作用。在这里，我们研究了在 Eurycoma longifolia Jack 提取物中发现的 quassinoid 之一——eurycomanone 对 A549 肺癌细胞选定基因表达的影响。eurycomanone 以 5 至 20μg/ml 的浓度范围以剂量依赖性方式抑制 A549 肺癌细胞增殖，抑制 50%细胞生长的浓度（GI（50））为 5.1μg/ml。在去除 eurycomanone 后，抗增殖作用并未完全逆转，其中仍有 30%的细胞抑制作用（p<0.0001，T 检验）。在 8μg/ml（GI（70））时，eurycomanone 通过软琼脂集落形成测定法抑制 A549 细胞的锚定非依赖性生长>25%（p<0.05，T 检验，n=8）。另一方面，顺铂是一种用于治疗非小细胞肺癌的化疗药物，其在 0.2μg/ml 至 15μg/ml 的浓度范围内抑制 A549 细胞增殖，GI（50）为 0.58μg/ml。eurycomanone 的治疗降低了肺癌标志物异质性核核糖核蛋白（hnRNP）A2/B1、p53 肿瘤抑制蛋白和其他与癌症相关的基因（包括 prohibitin（PHB）、膜联蛋白 1（ANX1）和内质网蛋白 28（ERp28））的丰度表达，但不包括管家基因。在用 5-20μg/ml 的可行治疗浓度处理 72 小时后，除 PHB 外，所有基因的 mRNA 表达均显著下调（p<0.05，T 检验，n=9）。这些发现表明，eurycomanone 在 5-20μg/ml 的可行治疗浓度下表现出对 A549 肺癌细胞的显著抗增殖和抗集落形成细胞生长作用。该治疗还导致抑制肺癌细胞肿瘤标志物和几种已知的癌细胞生长相关基因。
