Schupp Peter J, Kohlert-Schupp Claudia, Whitefield Susanna, Engemann Anna, Rohde Sven, Hemscheidt Thomas, Pezzuto John M, Kondratyuk Tamara P, Park Eun-Jung, Marler Laura, Rostama Bahman, Wright Anthony D
Marine Laboratory, University of Guam, Mangilao, Guam 96923.
Nat Prod Commun. 2009 Dec;4(12):1717-28.
The cancer chemopreventive and cytotoxic properties of 50 extracts derived from Twilight Zone (50-150 m) sponges, gorgonians and associated bacteria, together with 15 extracts from shallow water hard corals, as well as 16 fractions derived from the methanol solubles of the Twilight Zone sponge Suberea sp, were assessed in a series of bioassays. These assays included: Induction of quinone reductase (QR), inhibition of TNF-alpha activated nuclear factor kappa B (NFkappaB), inhibition of aromatase, interaction with retinoid X receptor (RXR), inhibition of nitric oxide (NO) synthase, inhibition 2,2-diphenyl-1-picrylhydrazyl radical scavenging (DPPH), and inhibition of HL-60 and MCF-7 cell proliferation. The results of these assays showed that at least 10 extracts and five fractions inhibited NFkappaB by greater than 60%, two extracts and two fractions inhibited DPPH by more than 50%, nine extracts and two fractions affected the survival of HL-60 cells, no extracts or fractions affected RXR, three extracts and six fractions affected quinone reductase (QR), three extracts and 12 fractions significantly inhibited aromatase, four extracts and five fractions inhibited nitric oxide synthase, and one extract and no fractions inhibited the growth of MCF-7 cells by more than 95%. These data revealed the tested samples to have many and varied activities, making them, as shown with the extract of the Suberea species, useful starting points for further fractionation and purification. Moreover, the large number of samples demonstrating activity in only one or sometimes two assays accentuates the potential of the Twilight Zone, as a largely unexplored habitat, for the discovery of selectively bioactive compounds. The overall high hit rate in many of the employed assays is considered to be a significant finding in terms of "normal" hit rates associated with similar samples from shallower depths.
对采自海洋中层带（50 - 150米）的海绵、柳珊瑚及相关细菌的50种提取物、15种浅水硬珊瑚提取物以及海洋中层带海绵Suberea sp甲醇可溶部分的16个组分进行了一系列生物活性测定，评估其癌症化学预防和细胞毒性特性。这些测定包括：醌还原酶（QR）诱导、肿瘤坏死因子-α激活的核因子κB（NFκB）抑制、芳香化酶抑制、视黄酸X受体（RXR）相互作用、一氧化氮（NO）合酶抑制、2,2 - 二苯基 - 1 - 苦基肼自由基清除（DPPH）抑制以及HL - 60和MCF - 7细胞增殖抑制。这些测定结果显示，至少10种提取物和5个组分对NFκB的抑制率大于60%，2种提取物和2个组分对DPPH的抑制率超过50%，9种提取物和2个组分影响HL - 60细胞存活，没有提取物或组分影响RXR，3种提取物和6个组分影响醌还原酶（QR），3种提取物和12个组分显著抑制芳香化酶，4种提取物和5个组分抑制一氧化氮合酶，1种提取物且无组分对MCF - 7细胞生长的抑制率超过95%。这些数据表明所测试的样品具有多种不同的活性，正如Suberea属提取物所示，使其成为进一步分离和纯化的有用起始材料。此外，大量仅在一种或有时两种测定中显示活性的样品突出了海洋中层带作为一个很大程度上未被探索的栖息地在发现选择性生物活性化合物方面的潜力。就与来自较浅深度的类似样品相关的“正常”命中率而言，许多所采用测定中的总体高命中率被认为是一个重要发现。
