SCREENING CULTURED MARINE MICROALGAE FOR ANTICANCER-TYPE ACTIVITY

SCREENING CULTURED MARINE MICROALGAE FOR ANTICANCER-TYPE ACTIVITY
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DOI:
10.1007/bf02186068
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发表时间:
1994-04-01
影响因子:
3.3
通讯作者:
CHEN, JL
CHEN, JL
中科院分区:
生物学3区
文献类型:
--
作者:
GERWICK, WH;ROBERTS, MA;CHEN, JL

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海洋蓝藻和其他海洋微藻是一种很有前景的新型抗癌天然产物来源。自然界中不形成席状或簇状的微观形态必须进行培养,以获得足够大小的样品。在热带潮间带和浅层潮下环境中进行微藻野外采集,采用手工采集和操作技术,将微藻装入小体积宽口罐中。实验室环境中的驯化时间对于将新种引入栽培很重要。琼脂平板上的操作为获得单藻培养提供了最佳成功率;有时这些是直接获得的无性系。这些纯菌株在3l的初始体积中培养,为药理学筛选提供足够的材料。在一系列基于机制的抗癌筛选中,包括蛋白激酶C (PKC)、蛋白tryosine激酶(PTK)和肌苷单磷酸脱氢酶(IMPDH),对提取物进行了评估。在这三个检测区域中筛选了超过501个提取物,其中23个对IMPDH有活性,9个对PKC有活性,9个对PTK有活性。对一种对PTK有活性的培养微藻(Poteriochromonas malhamensis)的萃取物制备了一种新型的氯磺酸脂,并对其结构进行了讨论。未来的努力将(a)针对尚未被充分探索的微藻群体,包括一些蓝藻目以及隐藻和chrysophytes的野外收集,以及(b)补充基于机制的筛选与癌细胞细胞毒性筛选。
Marine Cyanophyceae, and to a lesser extent other marine microalgae, are a promising source of new anticancer-type natural products. Microscopic forms that do not form mats or tufts in nature must be cultured in order to obtain sufficiently sized samples. Field collections of microalgae in intertidal and shallow subtidal tropical environments utilize hand collection and manipulation techniques into small-volume wide-mouth jars. Acclimation times in the laboratory environment are important in bringing new cultures into cultivation. Manipulation on agar plates has given the best success rate for obtaining unialgal cultures; sometimes these are obtained directly as axenic clones. These pure strains are cultured in an initial volume of 3 L to give sufficient material for pharmacological screening. The extracts are evaluated in a series of mechanism-based anticancer screens, including protein kinase C (PKC), protein tryosine kinase (PTK) and inosine monophosphate dehydrogenase (IMPDH). More that 501 extracts have been screened in these three assay areas, and have yielded 23 active to IMPDH, 9 to PKC, and 9 to PTK. The extract of one cultured microalga which was active to PTK, Poteriochromonas malhamensis, has yielded a novel chlorosulfolipid, whose structure is discussed. Future efforts will (a) target less well explored groups of microalgae including several orders of cyanophyceae as well as field collections of cryptophytes and chrysophytes, and (b) complement mechanism-based screening with cancer cell cytotoxicity screening.