El-Menshawi Bassem S, Fayad Walid, Mahmoud Khaled, El-Hallouty Salwa M, El-Manawaty May, Olofsson Maria Hägg, Linder Stig
Department of Pharmacognosy, Pharmaceutical Sciences Division, National Research Centre, Dokki, Giza 12622, Egypt.
Indian J Exp Biol. 2010 Mar;48(3):258-64.
Most of the currently used cancer therapeutics are natural products. These agents were generally discovered based on their toxicity to tumour cells using various bioassays. Although the exact mechanisms of action of the most commonly used cancer therapeutics such as anthracyclins, podophyllotoxins and camptothecin are incompletely understood, it is becoming increasingly clear that these agents often show complex modes of action at the cellular level, interacting with numerous targets. Such complex modes of action may be the very reason for clinical efficacy. For discovering new cytotoxic anticancer drugs sophisticated screening methods were used. The principles of such screening projects conducted, using collections of purified natural products or extracts from plants have been described. By performing simple but robust prescreening tests such as the brine shrimp assay, bioactive extracts can be identified. Extracts (65) prepared from a collection of Egyptian plants were identified that showed cytotoxity on HepG2 cells. Interestingly, 22 (33%) of these raw extracts, induced > 2-fold induction of caspase-cleavage activity in a colon carcinoma cell line, consistent with induction of apoptosis. Only a fraction of the diversity of the biosphere has been tested for biological activity and novel cancer therapeutics remains to be discovered.
目前使用的大多数癌症治疗药物都是天然产物。这些药物通常是基于它们对肿瘤细胞的毒性，通过各种生物测定法发现的。尽管最常用的癌症治疗药物如蒽环类抗生素、鬼臼毒素和喜树碱的确切作用机制尚未完全了解，但越来越清楚的是，这些药物在细胞水平上通常表现出复杂的作用模式，与众多靶点相互作用。这种复杂的作用模式可能正是其临床疗效的原因。为了发现新的细胞毒性抗癌药物，人们使用了复杂的筛选方法。已经描述了使用纯化天然产物或植物提取物进行此类筛选项目的原则。通过进行简单但可靠的预筛选试验，如卤虫试验，可以鉴定出生物活性提取物。从埃及植物收集物中制备的提取物（65种）被鉴定出对HepG2细胞具有细胞毒性。有趣的是，这些粗提物中有22种（33%）在结肠癌细胞系中诱导了>2倍的半胱天冬酶切割活性诱导，这与细胞凋亡的诱导一致。只有一小部分生物圈的多样性被测试了生物活性，新型癌症治疗药物仍有待发现。
