Max Planck Institute of Psychiatry, Clinical Neuroendocrinology Group, Kraepelinstr 10, 80804 Munich, Germany.
J Neurooncol. 2013 Jul;113(3):385-96. doi: 10.1007/s11060-013-1148-9. Epub 2013 May 11.
Meningiomas, the most frequent benign intracranial and intraspinal types of tumors are normally removed by surgery. Complications can occur when the tumor is critically localized and cannot be completely removed or when comorbidities of the mostly elder patients increase the general surgical risk. Thus, alternate medical treatment concepts for the therapy of meningiomas would be desirable. Curcumin, the active ingredient of the spice plant Curcuma longa has shown anti-tumorigenic actions in many different types of tumors and therefore, its effect on growth and apoptosis of meningioma cells was studied in the present paper. In vitro, treatment of the human Ben-Men-1 meningioma cell line and of a series of 21 primary human meningioma cell cultures with curcumin (1-20 μM) strongly reduced the proliferation in all cases in a dose dependent manner. Cell cycle analysis by fluorescence-activated cell sorting showed growth arrest at G2/M phase, which was confirmed by demonstrating the corresponding modulation of proteins involved in G2/M arrest by immunoblotting and/or confocal laser microscopy. High dosages (20, 50 μM) of curcumin induced a significant increase of apoptosis in Ben-Men-1 and primary meningioma cell cultures as demonstrated by morphological changes of cell nuclei, DNA fragmentation, translocation of cell membrane associated phosphatidyl serine and the induction of apoptotic-acting cleaved caspase-3. Our results suggest that the multi-targeting drug curcumin has potent anti-tumorigenic actions in meningioma cells and might therefore be a putative candidate for the pharmacological treatment of meningiomas.
脑膜瘤是最常见的颅内和脊髓良性肿瘤类型,通常通过手术切除。当肿瘤位置关键且无法完全切除,或大多数老年患者的合并症增加了一般手术风险时,可能会出现并发症。因此,脑膜瘤的治疗需要替代的医疗治疗方案。姜黄素是姜黄植物的活性成分,已在许多不同类型的肿瘤中显示出抗肿瘤作用,因此,本文研究了其对脑膜瘤细胞生长和凋亡的影响。在体外,用姜黄素(1-20 μM)处理人 Ben-Men-1 脑膜瘤细胞系和一系列 21 个人类原发性脑膜瘤细胞培养物,强烈地以剂量依赖的方式降低了所有情况下的增殖。通过荧光激活细胞分选进行细胞周期分析表明,G2/M 期出现生长停滞,通过免疫印迹和/或共聚焦激光显微镜证实了参与 G2/M 停滞的相应蛋白的调节来证实。高剂量(20、50 μM)的姜黄素诱导 Ben-Men-1 和原发性脑膜瘤细胞培养物中明显增加细胞凋亡,如细胞核形态变化、DNA 片段化、细胞膜相关磷脂酰丝氨酸的易位以及诱导凋亡的裂解 caspase-3 的诱导。我们的结果表明,多靶点药物姜黄素对脑膜瘤细胞具有强大的抗肿瘤作用,因此可能是脑膜瘤治疗的潜在候选药物。