Whibley Catherine E, Keyzers Robert A, Soper Andrew G, Davies-Coleman Michael T, Samaai Toufiek, Hendricks Denver T
Division of Medical Biochemistry, University of Cape Town, Medical School, Anzio Road, Observatory, Cape Town, 7925, South Africa.
Ann N Y Acad Sci. 2005 Nov;1056:405-12. doi: 10.1196/annals.1352.031.
Squamous cell esophageal cancer presents a significant health burden in many developing countries around the world. In South Africa, this disease is one of the most common causes of cancer-related deaths in black males. Because this cancer is only modestly responsive to available chemotherapeutic agents, there is a need to develop more effective therapeutic agents for this cancer. Marine organisms are currently regarded as a promising source of unique bioactive molecules because they display a rich diversity of secondary metabolites. Some of these compounds have significant anticancer activity, with a few of these currently in phase I and II clinical trials. We report here an ongoing program to screen marine organisms collected from subtidal benthic communities off the coast of southern Africa for activity against cultured esophageal cancer cells. Of the 137 extracts tested, 2.2% displayed high activity (score = 3) and 11.7% displayed moderate activity (score = 2) against cultured esophageal cancer cells. Our results suggest that sponges had a higher hit rate (21.9%) than ascidians (7.1%). Using activity-directed purification, seven previously described compounds and four novel compounds, with varying activity against esophageal cancer cell lines, were isolated from the sponges Axinella weltneri, Aplysilla sulphurea, and Strongylodesma aliwaliensis. The results of this study suggest that subtidal benthic marine organisms collected off the coast of southern Africa hold potential for identifying possible drug leads for the development of agents with activity against esophageal cancer.
鳞状细胞食管癌在世界上许多发展中国家造成了重大的健康负担。在南非,这种疾病是黑人男性癌症相关死亡的最常见原因之一。由于这种癌症对现有的化疗药物反应有限,因此需要开发更有效的治疗药物。海洋生物目前被认为是独特生物活性分子的一个有前景的来源,因为它们展示了丰富多样的次生代谢产物。其中一些化合物具有显著的抗癌活性,目前有几种正处于I期和II期临床试验阶段。我们在此报告一项正在进行的计划,该计划旨在筛选从非洲南部海岸潮下带底栖生物群落收集的海洋生物对培养的食管癌细胞的活性。在测试的137种提取物中,2.2%对培养的食管癌细胞显示出高活性(评分=3),11.7%显示出中等活性(评分=2)。我们的结果表明,海绵的命中率(21.9%)高于海鞘(7.1%)。通过活性导向纯化,从海绵Axinella weltneri、Aplysilla sulphurea和Strongylodesma aliwaliensis中分离出七种先前描述的化合物和四种新型化合物,它们对食管癌细胞系具有不同的活性。这项研究的结果表明,从非洲南部海岸收集的潮下带底栖海洋生物具有识别可能的药物先导物的潜力,这些先导物可用于开发对食管癌有活性的药物。