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首頁> 美國衛(wèi)生研究院文獻(xiàn)>Marine Drugs >Spongiatriol Inhibits Nuclear Factor Kappa B Activation and Induces Apoptosis in Pancreatic Cancer Cells
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Spongiatriol Inhibits Nuclear Factor Kappa B Activation and Induces Apoptosis in Pancreatic Cancer Cells

機(jī)譯：海綿三醇抑制核因子κB活化并誘導(dǎo)胰腺癌細(xì)胞凋亡。

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Pancreatic cancer, the fourth leading cause of cancer death in the US, is highly resistant to all current chemotherapies, and its growth is facilitated by chronic inflammation. The majority of pro-inflammatory cytokines initiate signaling cascades that converge at the activation of the Nuclear Factor Kappa B (NFκB), a signal transduction molecule that promotes cell survival, proliferation and angiogenesis. In an effort to identify novel inhibitors of NFκB, the HBOI library of pure compounds was screened using a reporter cell line that produces luciferin under the transcriptional control of NFκB. Seven compounds were identified through this screen, but in the case of five of them, their reported mechanism of action made them unlikely to be specific NFκB inhibitors. Spongiatriol, a marine furanoditerpenoid that was first isolated in the 1970s, is shown here to inhibit NFκB transcriptional activity in a reporter cell line, to reduce levels of phosphorylated (active) NFκB in the AsPC-1 cell line, to have an IC50 for cytotoxicity in the low micromolar range against the AsPC-1, BxPC-3, MiaPaCa-2 and Panc-1 pancreatic cancer cell lines, and to induce moderate but significant apoptosis in both the AsPC-1 and the Panc-1 cell lines.
機(jī)譯：胰腺癌是美國癌癥死亡的第四大主要原因，它對(duì)目前的所有化學(xué)療法均具有高度耐藥性，慢性炎癥促進(jìn)其生長。大多數(shù)促炎性細(xì)胞因子會(huì)啟動(dòng)信號(hào)級(jí)聯(lián)，這些級(jí)聯(lián)在核因子κB（NFκB）的激活時(shí)會(huì)聚，NFκB是促進(jìn)細(xì)胞存活，增殖和血管生成的信號(hào)轉(zhuǎn)導(dǎo)分子。為了鑒定新的NFκB抑制劑，使用在NFκB轉(zhuǎn)錄控制下產(chǎn)生熒光素的報(bào)告細(xì)胞株篩選了純化合物的HBOI文庫。通過此篩選可鑒定出7種化合物，但對(duì)于其中5種，據(jù)報(bào)道其作用機(jī)理使其不太可能成為特定的NFκB抑制劑。 Spongiatriol是一種海洋呋喃二萜類化合物，于1970年代首次分離出來，在這里顯示它可以抑制報(bào)告細(xì)胞中的NFκB轉(zhuǎn)錄活性，從而降低AsPC-1細(xì)胞系中磷酸化（活性）NFκB的水平，從而具有IC50的細(xì)胞毒性作用在低微摩爾范圍內(nèi)針對(duì)AsPC-1，BxPC-3，MiaPaCa-2和Panc-1胰腺癌細(xì)胞系，并在AsPC-1和Panc-1細(xì)胞系中誘導(dǎo)中等但重要的凋亡。

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