Inhibition of cellular proliferation and induction of apoptosis by curcumin in human malignant astrocytoma cell lines
Inhibition of cellular proliferation and induction of apoptosis by curcumin in human malignant astrocytoma cell lines
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DOI：
10.1007/s11060-004-5757-1
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发表时间：
2005-09-01
影响因子：
3.9
通讯作者：
Endo, S
中科院分区：
文献类型：
--
作者：
Nagai, S;Kurimoto, M;Endo, S
已知核因子（NF）-κ B控制细胞增殖和凋亡。在恶性星形细胞瘤细胞中，NF-κ B B被异常激活并促进其增殖。因此，抑制NF-κ B活性被认为是恶性星形细胞瘤的一种有前途的治疗策略。最近，姜黄素，姜黄的主要成分，被报道抑制NF-κ B B活性。在这项研究中，我们研究了姜黄素对NF-κ B B活性和细胞增殖的抑制作用，以及姜黄素对人恶性星形细胞瘤细胞系的凋亡诱导作用。采用电泳迁移率改变法检测姜黄素对NP-2人恶性星形细胞瘤细胞株NF-κ B B活性的影响。用[H-3]胸苷掺入法和台盼蓝拒染法分别检测了姜黄素对5株人恶性星形细胞瘤细胞DNA合成和细胞生长的影响。应用DNA片段化分析和形态学观察，研究姜黄素诱导NP-2和NP-3人恶性星形细胞瘤细胞凋亡的作用。我们发现，NF-κ B B活性在NP-2显着降低姜黄素。姜黄素对5种恶性星形细胞瘤细胞株的DNA合成和细胞生长均有抑制作用，且呈剂量依赖性。用姜黄素处理后，NP-2和NP-3中均观察到核浓缩和断裂，以及DNA断裂。这些结果表明，姜黄素抑制恶性星形细胞瘤细胞系的细胞增殖和诱导凋亡。这些结果被认为是姜黄素抑制NF-κ B活性的结果。
Nuclear factor (NF)-kappa B is known to control cellular proliferation and apoptosis. In malignant astrocytoma cells, it was reported that NF-kappa B was activated aberrantly and promoted their proliferation. Thus, inhibition of NF-kappa B activity is considered to be a promising therapeutic strategy for malignant astrocytoma. Recently, curcumin, the major constituent of turmeric, was reported to inhibit NF-kappa B activity. In this study, we investigated inhibitory effects of curcumin on NF-kappa B activity and cellular proliferation, and induction of apoptosis by curcumin in human malignant astrocytoma cell lines. Alteration of NF-kappa B 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 [H-3]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-kappa B 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-kappa B activity by curcumin.