School of Health and Social Sciences, Department of Natural Sciences, Middlesex University, Hendon, The Burroughs, London, UK.
Oncol Rep. 2012 Oct;28(4):1435-42. doi: 10.3892/or.2012.1941. Epub 2012 Jul 27.
Malignant brain tumours are rare but are the most challenging types of cancers to treat. Despite conventional multimodality approaches available for their management, the outlook for most patients remains dismal due to the ability of the tumour cells to invade the normal brain. Attention has now focused on novel therapeutic interventions such as as the use of micronutrients. Both chokeberry extract (Aronia melanocarpa), which is rich in natural pigments such as anthocyanins and curcumin (diferuloylmethane) found in turmeric (Curcuma longa) have been reported to possess anticancer properties in other cancers. The aim of this study was to extend our previous research to evaluate the therapeutic potential of these two agents by testing their ability to induce apoptosis in an established glioblastoma cell line (U373). This was accomplished by treating the cells for 48 h with either chokeberry extract or curcumin, and using the Annexin-V assay. Gene profiles of 8 MMPs (2, 9, 14, 15, 16, 17, 24 and 25) and 4 TIMPs (1, 2, 3 and 4) were analysed for effects of mediators of invasion by quantitative real-time polymerase chain reaction (RT-PCR). The IC50 values determined for curcumin and chokeberry extract were 15 and 200 µg/ml, respectively. Our results also suggest that curcumin induces apoptosis but chokeberry extract is necrotic to this cell line. It is possible that chokeberry extract kills the cells by other non-apoptotic pathways. In addition, the RT-PCR results show downregulation of the gene expression of MMP-2, -14, -16 and -17 for both micronutrients. Taken together, the comparative data suggest that both curcumin and chokeberry extract may exhibit their anticancer potential by inducing apoptosis and inhibiting invasion by reducing MMP gene expression.
恶性脑肿瘤较为罕见，但却是最难治疗的癌症类型之一。尽管目前有多种常规的多模式方法可用于治疗此类疾病，但由于肿瘤细胞具有侵袭正常大脑的能力，大多数患者的预后仍然不容乐观。现在，人们的注意力集中在新的治疗干预措施上，如使用微量营养素。此前有研究报道，黑树莓提取物（Aronia melanocarpa）富含天然色素，如花色苷和姜黄素（二芳基庚烷），在其他癌症中具有抗癌特性。姜黄（Curcuma longa）中的姜黄素也具有抗癌特性。本研究旨在扩展我们之前的研究，通过测试这两种药物在已建立的神经胶质瘤细胞系（U373）中诱导细胞凋亡的能力，来评估这两种药物的治疗潜力。为此，用黑树莓提取物或姜黄素处理细胞 48 小时，然后用 Annexin-V 测定法进行处理。通过定量实时聚合酶链反应（RT-PCR）分析 8 种 MMPs（2、9、14、15、16、17、24 和 25）和 4 种 TIMPs（1、2、3 和 4）的基因谱，以分析侵袭相关介质的作用。确定姜黄素和黑树莓提取物的 IC50 值分别为 15 和 200μg/ml。我们的结果还表明，姜黄素诱导细胞凋亡，而黑树莓提取物对该细胞系具有细胞坏死作用。黑树莓提取物通过其他非细胞凋亡途径杀死细胞的可能性是存在的。此外，RT-PCR 结果显示，这两种微量营养素均下调 MMP-2、-14、-16 和 -17 的基因表达。综上所述，比较数据表明，姜黄素和黑树莓提取物可能通过诱导细胞凋亡和抑制 MMP 基因表达来抑制侵袭，从而发挥其抗癌潜力。
