Ardalani Hamidreza, Avan Amir, Ghayour-Mobarhan Majid
Department of Horticultural Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Metabolic Syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Avicenna J Phytomed. 2017 Jul-Aug;7(4):285-294.
The aim of the present review is to give an overview about the role, biosynthesis, and characteristics of Podophyllotoxin (PTOX) as a potential antitumor agent with particular emphasis on key biosynthesis processes, function of related enzymes and characterization of genes encoding the enzymes.
Google scholar, PubMed and Scopus were searched for literatures which have studied identification, characterization, fermentation and therapeutic effects of PTOX and published in English language until end of 2016.
PTOX is an important plant-derived natural product, has derivatives such as etoposide and teniposide, which have been used as therapies for cancers and venereal wart. PTOX structure is closely related to the aryltetralin lactone lignans that have antineoplastic and antiviral activities. Wall. (syn. ) and L. (Berberidaceae) are the major sources of PTOX. It has been shown that ferulic acid and methylenedioxy substituted cinnamic acid are the enzymes involved in PTOX synthesis. PTOX prevents cell growth via polymerization of tubulin, leading to cell cycle arrest and suppression of the formation of the mitotic-spindles microtubules.
Several investigations have been performed in biosynthesis of PTOX such as cultivation of these plants, though they were unsuccessful. Thus, it is important to find alternative sources to satisfy the pharmaceutical demand for PTOX. Moreover, further preclinical studies are warranted to explore the molecular mechanisms of these agents in treatment of cancer and their possible potential to overcome chemoresistance of tumor cells.
本综述旨在概述鬼臼毒素（PTOX）作为一种潜在抗肿瘤药物的作用、生物合成及特性，特别强调关键生物合成过程、相关酶的功能以及编码这些酶的基因的特征。
检索谷歌学术、PubMed和Scopus数据库，查找截至2016年底发表的、以英文撰写的关于PTOX的鉴定、特性、发酵及治疗效果的研究文献。
PTOX是一种重要的植物源天然产物，有依托泊苷和替尼泊苷等衍生物，已被用作癌症和尖锐湿疣的治疗药物。PTOX的结构与具有抗肿瘤和抗病毒活性的芳基四氢萘内酯木脂素密切相关。鬼臼属（syn.）和小檗科的桃儿七属（L.）是PTOX的主要来源。已表明阿魏酸和亚甲二氧基取代的肉桂酸是参与PTOX合成的酶。PTOX通过微管蛋白聚合阻止细胞生长，导致细胞周期停滞并抑制有丝分裂纺锤体微管的形成。
尽管在PTOX生物合成方面已经进行了一些研究，如种植这些植物，但均未成功。因此，找到替代来源以满足对PTOX的药物需求很重要。此外，有必要进行进一步的临床前研究，以探索这些药物治疗癌症的分子机制及其克服肿瘤细胞化疗耐药性的潜在可能性。
