Kareh Mike, El Nahas Rana, Al-Aaraj Lamis, Al-Ghadban Sara, Naser Al Deen Nataly, Saliba Najat, El-Sabban Marwan, Talhouk Rabih
Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Beirut, Lebanon.
Nature Conservation Center, American University of Beirut, Beirut, Lebanon.
SAGE Open Med. 2018 Nov 2;6:2050312118809541. doi: 10.1177/2050312118809541. eCollection 2018.
Sea cucumbers are considered among the most important functional foods. Following bioassay guided fractionation, we assessed the anti-proliferative and anti-inflammatory activities of () extracts.
Sea cucumber ethanolic extract and the partially purified aqueous fractions were assessed for their anti-proliferative activities. These latter bioactivities were evaluated in the highly invasive MDA-MB-231 human breast cancer cells in two-dimensional and three-dimensional cultures using trypan blue exclusion assay. The tumor-suppressive effects of sea cucumber ethanolic extract and aqueous fractions were assayed by measuring the trans-well invasion of MDA-MB-231 cells and the expression of some epithelial mesenchymal transition markers using quantitative reverse-transcription polymerase chain reaction and western blot analysis. The anti-inflammatory activity of the aqueous fraction was tested by measuring the secreted levels of interleukin-6, nitric oxide, and matrix metalloproteinase 9 in endotoxin-induced mammary epithelial SCp2 cells and interleukin-1β in phorbol-12-myristate-13-acetate-activated human monocytic THP-1 cells.
Sea cucumber ethanolic extract and the aqueous fraction significantly decreased the proliferation of MDA-MB-231 cells by more than 50% at similar and noncytotoxic concentrations and caused an arrest in the S-phase of the cell cycle of treated cells. In contrast, petroleum ether, chloroform, ethyl acetate, and -butanol organic fractions did not show any significant activity. Furthermore, sea cucumber ethanolic extract and aqueous fraction reduced the proliferation of MDA-MB-231 cells in three-dimensional cultures by more than 60% at noncytotoxic concentrations. In addition, treatment with these concentrations resulted in the loss of stellate outgrowths in favor of spherical aggregates and a 30% decrease in invasive properties. Both sea cucumber ethanolic extract and aqueous decreased the transcription of vimentin and the protein expression levels of vimentin and N-cadherin in three-dimensional cultures. The aqueous fraction decreased the levels of inflammatory markers interleukin-6, nitric oxide, and matrix metalloproteinase 9 in the mouse mammary SCp2 cells, and the level of interleukin-1β produced by phorbol-12-myristate-13-acetate-activated THP-1 human monocytic cells.
The data reveal for the first time promising anti-proliferative and anti-inflammatory activities in water extract in two-dimensional and three-dimensional culture models.
海参被认为是最重要的功能性食品之一。在生物测定指导下进行分级分离后，我们评估了（）提取物的抗增殖和抗炎活性。
评估海参乙醇提取物和部分纯化的水相馏分的抗增殖活性。使用台盼蓝排斥试验，在二维和三维培养的高侵袭性MDA-MB-231人乳腺癌细胞中评估这些生物活性。通过测量MDA-MB-231细胞的跨膜侵袭以及使用定量逆转录聚合酶链反应和蛋白质印迹分析来检测一些上皮-间质转化标志物的表达，测定海参乙醇提取物和水相馏分的肿瘤抑制作用。通过测量内毒素诱导的乳腺上皮SCp2细胞中白细胞介素-6、一氧化氮和基质金属蛋白酶9的分泌水平以及佛波醇-12-肉豆蔻酸酯-13-乙酸酯激活的人单核细胞THP-1细胞中白细胞介素-1β的水平，测试水相馏分的抗炎活性。
海参乙醇提取物和水相馏分在相似且无细胞毒性的浓度下使MDA-MB-231细胞的增殖显著降低超过50%，并导致处理细胞的细胞周期在S期停滞。相比之下，石油醚、氯仿、乙酸乙酯和正丁醇有机馏分未显示任何显著活性。此外，海参乙醇提取物和水相馏分在无细胞毒性浓度下使三维培养的MDA-MB-231细胞的增殖降低超过60%。此外，用这些浓度处理导致星状突起消失，有利于球形聚集体形成，侵袭特性降低30%。海参乙醇提取物和水相馏分均降低了三维培养中波形蛋白的转录以及波形蛋白和N-钙黏蛋白的蛋白表达水平。水相馏分降低了小鼠乳腺SCp2细胞中炎症标志物白细胞介素-6、一氧化氮和基质金属蛋白酶9的水平，以及佛波醇-12-肉豆蔻酸酯-13-乙酸酯激活的THP-1人单核细胞产生的白细胞介素-1β水平。
数据首次揭示了在二维和三维培养模型中，（）水提取物具有有前景的抗增殖和抗炎活性。
