Nagai Shoichi, Kurimoto Masanori, Washiyama Kazuo, Hirashima Yutaka, Kumanishi Toshiro, Endo Shunro
Department of Neurosurgery, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
J Neurooncol. 2005 Sep;74(2):105-11. doi: 10.1007/s11060-004-5757-1.
Nuclear factor (NF)-kappaB is known to control cellular proliferation and apoptosis. In malignant astrocytoma cells, it was reported that NF-kappaB was activated aberrantly and promoted their proliferation. Thus, inhibition of NF-kappaB activity is considered to be a promising therapeutic strategy for malignant astrocytoma. Recently, curcumin, the major constituent of turmeric, was reported to inhibit NF-kappaB activity. In this study, we investigated inhibitory effects of curcumin on NF-kappaB activity and cellular proliferation, and induction of apoptosis by curcumin in human malignant astrocytoma cell lines. Alteration of NF-kappaB activity in NP-2 human malignant astrocytoma cell line after treatment with curcumin was examined using electrophoretic mobility shift assay. Alterations of DNA synthesis and cellular growth in five human malignant astrocytoma cell lines after treatment with curcumin were examined using [(3)H]thymidine incorporation assay and the trypan blue dye exclusion method, respectively. Induction of apoptosis by curcumin in NP-2 and NP-3 human malignant astrocytoma cell lines was examined by DNA-fragmentation analysis and morphological observation. We found that the NF-kappaB activity in NP-2 was significantly reduced by curcumin. The DNA synthesis and the cellular growth were inhibited by curcumin in dose-dependent manner in all the five malignant astrocytoma cell lines. Nuclear condensation and fragmentation, and DNA fragmentation were observed in both NP-2 and NP-3 after the treatment with curcumin. These results indicate that curcumin inhibits the cellular proliferation and induces apoptosis in human malignant astrocytoma cell lines. These results are considered to be resulted from the inhibition of NF-kappaB activity by curcumin.
核因子（NF）-κB可调控细胞增殖与凋亡。据报道，在恶性星形细胞瘤细胞中，NF-κB被异常激活并促进其增殖。因此，抑制NF-κB活性被认为是治疗恶性星形细胞瘤的一种有前景的策略。最近，有报道称姜黄素（姜黄的主要成分）可抑制NF-κB活性。在本研究中，我们调查了姜黄素对人恶性星形细胞瘤细胞系中NF-κB活性和细胞增殖的抑制作用，以及姜黄素诱导细胞凋亡的情况。使用电泳迁移率变动分析检测姜黄素处理后NP-2人恶性星形细胞瘤细胞系中NF-κB活性的变化。分别使用[³H]胸腺嘧啶核苷掺入法和台盼蓝拒染法检测姜黄素处理后五种人恶性星形细胞瘤细胞系中DNA合成和细胞生长的变化。通过DNA片段化分析和形态学观察检测姜黄素对NP-2和NP-3人恶性星形细胞瘤细胞系凋亡的诱导作用。我们发现姜黄素可显著降低NP-2中的NF-κB活性。在所有五种恶性星形细胞瘤细胞系中，姜黄素均以剂量依赖方式抑制DNA合成和细胞生长。姜黄素处理后，在NP-2和NP-3中均观察到核浓缩、核碎裂以及DNA片段化。这些结果表明，姜黄素可抑制人恶性星形细胞瘤细胞系中的细胞增殖并诱导细胞凋亡。这些结果被认为是姜黄素抑制NF-κB活性所致。
