Marine Natural Products as Inhibitors of Hypoxic Signaling in Tumors.
Marine Natural Products as Inhibitors of Hypoxic Signaling in Tumors.
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DOI：
10.1007/s11101-009-9120-1
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发表时间：
2009-06
期刊：
影响因子：
--
通讯作者：
Zhou YD
中科院分区：
文献类型：
--
作者：
Nagle DG;Zhou YD
海洋天然产物已成为发现潜在抗癌药物的新化学实体的主要来源，这些药物有效地抑制各种抗肿瘤分子靶标。由于血管化不足，在快速生长的实体瘤块内形成缺氧区域。这些低氧肿瘤细胞中基因表达的特异性改变有助于促进实体瘤的存活和转移扩散。对细胞缺氧的转录反应主要由转录因子缺氧诱导因子-1（HIF-1）介导，其调节参与缺氧应激下细胞适应和存活的100多个基因的表达。癌症患者的临床研究表明，HIF-1的激活与晚期疾病阶段和治疗抵抗直接相关。HIF-1已成为抗癌药物开发的重要肿瘤选择性分子靶点。因此，已经从植物和微生物中鉴定出基于天然产物的HIF-1活化抑制剂。最近，来自海绵、海百合和藻类的结构独特的天然产物已被鉴定为HIF-1活化抑制剂。美国国家癌症研究所的海洋无脊椎动物和藻类提取物开放库已被证明是天然产物HIF-1抑制剂的宝贵来源。在所鉴定的活性化合物中，某些海洋天然产物还显示出抑制HIF-1靶基因如血管内皮生长因子（VEGF）的缺氧诱导。其中一些海洋HIF-1抑制剂通过干扰缺氧细胞中线粒体信号分子的产生来发挥作用。然而，许多新发现的海洋天然产物HIF-1抑制剂的确切作用机制仍然没有得到解决。
Marine natural products have become a major source of new chemical entities in the discovery of potential anticancer agents that potently suppress various antitumor molecular targets. As a consequence of insufficient vascularization, hypoxic regions form within rapidly growing solid tumor masses. Specific alterations of gene expression in these hypoxic tumor cells help facilitate the survival and metastatic spread of solid tumors. The transcriptional response to cellular hypoxia is primarily mediated by the transcription factor hypoxia-inducible factor-1 (HIF-1) that regulates the expression of more than 100 genes involved in cellular adaptation and survival under hypoxic stress. Clinical studies in cancer patients indicate that HIF-1 activation is directly correlated with advanced disease stages and treatment resistance. HIF-1 has emerged as an important tumor-selective molecular target for anticancer drug discovery. As a result, natural product-based inhibitors of HIF-1 activation have been identified from plants and microorganisms. Recently, structurally unique natural products from marine sponges, crinoids, and algae have been identified as HIF-1 activation inhibitors. The US National Cancer Institute’s Open Repository of marine invertebrate and algae extracts has proven to be a valuable source of natural product HIF-1 inhibitors. Among the active compounds identified, certain marine natural products have also been shown to suppress the hypoxic induction of HIF-1 target genes such as vascular endothelial growth factor (VEGF). Some of these marine HIF-1 inhibitors act by interfering with the generation of mitochondrial signaling molecules in hypoxic cells. However, the precise mechanisms of action for many newly identified marine natural product HIF-1 inhibitors remain unresolved.
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影响因子：
5.1
作者：
Dai, Jingqiu;Liu, Yang;Nagle, Dale G.
通讯作者：
Nagle, Dale G.
DOI：
10.1073/pnas.0611662104
发表时间：
2007-05-29
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
8.8
作者：
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通讯作者：
D'Incalci, M
影响因子：
5.1
作者：
Dai, Jingqiu;Liu, Yang;Nagle, Dale G.
通讯作者：
Nagle, Dale G.
影响因子：
2.9
作者：
Ahuja, D;Vera, MD;Toogood, PL
通讯作者：
Toogood, PL