Growth inhibitory effects of obovatol through induction of apoptotic cell death in prostate and colon cancer by blocking of NF-κB
Growth inhibitory effects of obovatol through induction of apoptotic cell death in prostate and colon cancer by blocking of NF-κB
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DOI：
10.1016/j.ejphar.2007.12.027
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发表时间：
2008-03-17
影响因子：
5
通讯作者：
Hong, Jin Tae
中科院分区：
文献类型：
--
作者：
Lee, So Yong;Yuk, Dong Yeon;Hong, Jin Tae
厚朴中的双酚成分，包括厚朴酚和和厚朴酚，已显示出多种药理活性，例如抗肿瘤、抗氧化和抗炎作用。之前在培养的巨噬细胞 Raw264.7 细胞和成纤维细胞中，我们发现 obovatol（一种从 M. obovata 中分离出来的活性化合物）可抑制 NF-κ B 活性，而 NF-κ B 已知是控制癌细胞生长的重要转录因子。我们在这里研究了 obovatol 是否可以抑制 NF-kappa B 活性，从而抑制前列腺癌（LNCaP 和 PC-3）和结肠癌（SW620 和 HCT 116）细胞中的癌细胞生长。在肿瘤坏死因子-α（TNF-α，10 ng/ml）和十四烷酰佛波醇乙酸酯（TPA 10 或 50 nM）不存在或存在的情况下，obovatol（10、15、20、25 AM）治疗可通过诱导细胞凋亡，以浓度依赖性方式抑制癌细胞生长。使用高达 50 AM obovatol 时，在正常细胞中未观察到细胞毒性活性。还发现 obovatol 抑制 TNF-α 和 TPA 诱导的 NF-kappa B 转录和 DNA 结合活性。在进一步研究中，obovatol 通过减少 I kappa B 的磷酸化来减少 p65 和 p50 转入细胞核。obovatol 与诱导细胞凋亡密切相关，增加了凋亡基因的表达； Bax、caspase-3、caspase-9，而抑制抗凋亡基因的表达； Bcl-2、凋亡抑制蛋白（IAP-1）和X染色体IAP（XIAP）以及细胞增殖标志基因； Cox-2、c-Fos、c-Jun 和细胞周期蛋白 D1。这些结果表明，obovatol 通过诱导细胞凋亡来抑制前列腺癌细胞和结肠癌细胞的生长，并且抑制 NF-κ B 可能是其重要的作用机制。 (c) 2007 Elsevier B.V. 保留所有权利。
Biphenolic components in Magnolia obovata including magnolol and honokiol have shown several pharmacological activities such as antitumor, anti-oxidant and anti-inflammatory effects. Previously in cultured macrophage Raw264.7 cells and fibroblast, we found that obovatol, an active compound isolated from M. obovata inhibited NF-kappa B activity which has been known to be a significant transcriptional factor to control of cancer cell growth. We investigated here whether obovatol could inhibit NF-kappa B activity, and thereby inhibit cancer cell growth in prostate (LNCaP and PC-3) and colon cancer (SW620 and HCT 116) cells. Treatment of obovatol (10, 15, 20, 25 AM) inhibits cancer cell growth in the absence or the presence of tumor necrosis factor-alpha (TNF-alpha, 10 ng/ml) and tetradecanoyl phorbol acetate (TPA 10 or 50 nM) in a concentration-dependent manner through induction of apoptotic cell death. Cytotoxic activity was not observed in normal cells with up to 50 AM obovatol. It was also found that obovatol inhibited TNF-alpha and TPA-induced transcriptional and DNA binding activities of NF-kappa B. In further study, obovatol decreased translocation p65 and p50 into nucleus via decrease of phosphorylation of I kappa B. Correlated well with the induction of apoptosis, obovatol increased the expression of the apoptotic genes; Bax, caspase-3, caspase-9, whereas inhibited expression of anti-apoptotic genes; Bcl-2, inhibitor of apoptosis protein (IAP-1) and X chromosome IAP (XIAP) as well as the cell proliferation marker genes; Cox-2, c-Fos, c-Jun and cyclin D1. These results suggest that obovatol inhibits prostate and colon cancer cell growth via induction of apoptotic cell death, and that inhibition of NF-kappa B may be a significant as its action mechanism. (c) 2007 Elsevier B.V. All rights reserved.