癌症是全球疾病致死率的主要原因,寻找新的癌症治疗药物仍然是一个重要挑战,而海洋作为广阔的药物资源聚集地,具有非常丰富的抗肿瘤活性化合物,其中的一些海洋微藻被报道具有抗癌活性。
Cancer is the leading cause of death globally and finding new therapeutic agents for cancer treatment remains a major challenge in the pursuit for a cure, while the ocean, as a vast collection of drug resources, is very rich in antitumor active compounds, and some marine microalgae have been reported to have anticancer activity.
药物从被开发到生产需要经历漫长的过程,海洋微藻有其独特的特性使其拥有充满想象力的发展前景。尽管报道从海洋生物中分离出超过28,000种化合物,而且这个数字每年在迅速增长,直到20世纪中期,科学家才开始系统地探索海洋中的新药。如今一种分子从最初的研发管道到最后生产成已批准的治疗药物,要经历包括临床前测试、复杂的人体临床试验以及食品和药物管理局的试验后监管批准,需要10到15年,花费数千万美元。
It takes a long time for drugs to be developed and produced, and marine microalgae have unique properties that make them promising in the future development. To date, more than 28,000 compounds isolated from marine organisms have been reported, and this number is rapidly growing each year. However, despite the number of compounds isolated from marine organisms and the biological activities attributed to many of these, the search for ocean medicines is relatively recent and only in the middle part of the 20th century did scientists begin to systematically probe the oceans for new drugs. Today, the pipeline from the initial demonstration that a molecule may have therapeutic potential to the production of an approved drug involves pre-clinical testing, complex clinical trials in humans, and post-trial regulatory approval by the Food and Drug Administration (FDA). For drugs, this process can take 10 to 15 years and costs millions of dollars.
其中包括几个因素,如获得生物活性物质的困难、提取物中活性化合物数量少、找到足够的分离和纯化程序、化合物产生的可能毒性,化合物的可持续生产减缓整个管道的产出速度。尽管存在这些困难,新海洋药物的发现是当今海洋科学最有前途的新方向之一,微藻作为真核单细胞植物贡献了其全球40%的生产力。它们是色素、脂质、类胡萝卜素、欧米伽-3脂肪酸、多糖、维生素和其他精细化学物质的极好来源,同时微藻很容易在光生物反应器中培养以获得巨大的生物量,代表一种可再生的和仍未开发的药物发现资源。作为抗癌物质微藻也展现出其强大的抗肿瘤活性。下表报告了已显示出抗癌特性的微藻物种、受微藻影响的癌细胞系以及已被测试以诱导细胞生长停滞的浓度。
Several factors, such as difficulties in harvesting organisms, low quantities of active compounds in extracts, finding adequate procedures for isolation and purification, possible toxicity of the compounds and sustainable production of compounds may slow down the entire pipeline. Notwithstanding these difficulties, the discovery of new ocean medicines is one of the most promising new directions of marine science today. Microalgae are eukaryotic unicellular plants that contribute up to 40% of global primary productivity. They are excellent sources of pigments, lipids, carotenoids, omega-3 fatty acids, polysaccharides, vitamins and other fine chemicals. They can be easily cultivated in photo-bioreactors (e.g., in 100,000 L bioreactors) to obtain a huge biomass and represent a renewable and still poorly-explored resource for drug discovery. They use solar energy and fix CO2 which contributes to the mitigation of greenhouse gas effects and the removal of nitrogen and phosphorous derivatives which can be pollutants depending on their concentration. The following table reports the microalgal species that have shown anti-cancer properties, the cancer cell lines affected by microalgae and the concentrations that have been tested to induce the arrest of cell growth.
微藻中的活性成分包括椭圆小球藻的类胡萝卜素提取物、角毛藻属提取物、前黄藻的有机组分,前黄藻、共生菌、共生菌、马来菌、壶菌、腹壶菌和异孢菌的甲醇提取物、海洋骨骼藻的疏水组分、加拿大海洋微藻池的含水提取物、梭氏小球藻的含水提取物。
Active fractions from marine microalgae include carotenoid extract from chlorella ellipsoidea, ethanol and ethyl acetate extracts from chaetoceros calcitrans, organic fractions from amphidinium carterae, methanolic extracts from amphidinium carterae, prorocentrum rhathymum, symbiodinium sp., coolia malayensis, ostreopsis ovata, amphidinium operculatum and heterocapsa psammophila, hydrophobic fraction from skeletonema marinoi, aqueous extract from a canadian marine microalgal pool, and aqueous extract from chlorella sorokiniana.
而从微藻中分离出的几种化合物,不仅可以作为抗癌化合物来研究,而且作用于其他生物技术应用。多不饱和醛、二碳五烯酸(EPA)、岩藻黄质、紫黄质、柱甾醇或氯盐胺可能作为高价值产品(例如,营养品、化妆品、添加剂、燃料前体和生物材料)或未来可能的新药。
Several compounds isolated from microalgae have been studied not only as possible anti-cancer compounds, but also for other biotechnological applications. Compounds such as polyunsaturated aldehydes, eicosapentaenoic acid (EPA), fucoxanthin, violaxanthin, stigmasterol or chrysolaminaran may have a potential role as high-value products (e.g., nutraceuticals, cosmeceuticals, additives, fuel precursors and biomaterials) or as possible future new drugs.
例如,多不饱和醛对Caco-2、A549和Colo205癌细胞系显示出抗增殖活性,同时显示出的抗菌活性,使它们成为药物开发的新候选药物。多不饱和脂肪酸,EPA,作为一种营养或膳食补充剂已被广泛研究,对胎儿发育,预防心血管疾病,甚至改善阿尔茨海默病患者的认知功能有有益的影响;岩藻黄质已被证明具有潜在的抗炎、抗氧化、抗肥胖、抗糖尿病、抗瘤和心脏保护活性。在市场上,有几种基于岩藻黄质的产品被用作膳食补充剂,如“岩藻黄质特殊配方素食胶囊”或“Bri营养岩藻黄质胶囊”;植物甾醇如耻辱甾醇由于它们能够降低血液胆固醇浓度,预防一般的心血管疾病。烟甾醇不仅有抗癌活性,而且被研究证明其具有抗氧化活性。
For example, the polyunsaturated aldehydes have shown anti-proliferative activities on Caco-2, A549 and COLO 205 cancer cell lines, but also anti-bacterial activities, making them possible new candidates for drug development. The polyunsaturated fatty acid, EPA, has been widely studied as a nutraceutical or dietary supplement, with beneficial effects on fetal development, prevention of cardiovascular diseases and even, the improvement of cognitive functioning in patients with Alzheimer’s disease. Fucoxanthin has been shown to possess potential anti-inflammatory, antioxidant, anti-obesity, anti-diabetic, anti-tumorigenic and cardioprotective activities. On the market, there are several fucoxanthin-based products used as dietary supplements such as “Solaray Fucoxanthin Special Formula Vegetarian Capsules” or “BRI NUTRITION Fucoxanthin Capsules”. Phytosterols such as stigmasterol have been receiving increasing attention because of their capacity to reduce blood cholesterol concentrations, prevent cardiovascular disorders and because of their health benefits in general. Stigmasterol has been studied not only for its anti-cancer activity but also for its antioxidant activity.
这些数据强调,微藻可以成为一种很有前途的抗癌化合物来源。对于从海洋微藻中获得的其他组分/提取物,不能排除其在临床或生物技术方面的潜力,这需要进一步的研究来证明这种可能性。(简述翻译者:海南大学研究生申逸)
These data highlight that microalgae can be a promising source of anti-cancer compounds. Regarding the other fractions/extracts obtained from marine microalgae, it cannot be excluded that other compounds are present with clinical or biotechnological potential, but further studies are necessary to demonstrate this possibility.
来源:https://sci-hub.ru/10.3390/md16050165