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增强毛状根培养物中具有抗癌潜力的含氮代谢产物的生产。

Enhanced Production of Nitrogenated Metabolites with Anticancer Potential in Hairy Root Cultures.

机构信息

Federal Scientific Center of the East Asia Terrestrial Biodiversity of the Far East Branch of Russian Academy of Sciences, 159 Stoletija Str., 690022 Vladivostok, Russia.

Department of Medical Biology and Biotechnology, Far Eastern Federal University, 690950 Vladivostok, Russia.

出版信息

Int J Mol Sci. 2023 Jul 8;24(14):11240. doi: 10.3390/ijms241411240.

Abstract

is a relic liana, which is widely used in traditional Chinese herbal medicine and is endemic to the Manchurian floristic region. Since this plant is rare and slow-growing, alternative sources of its valuable compounds could be explored. Herein, we established hairy root cultures of transformed with root oncogenic loci ( and genes. The accumulation of nitrogenous secondary metabolites significantly improved in transgenic cell cultures. Specifically, the production of magnoflorine reached up to 5.72 mg/g of dry weight, which is 5.8 times higher than the control calli and 1.7 times higher than in wild-growing liana. Simultaneously, the amounts of aristolochic acids I and II, responsible for the toxicity of species, decreased by more than 10 fold. Consequently, the hairy root extracts demonstrated pronounced cytotoxicity against human glioblastoma cells (U-87 MG), cervical cancer cells (HeLa CCL-2), and colon carcinoma (RKO) cells. However, they did not exhibit significant activity against triple-negative breast cancer cells (MDA-MB-231). Our findings suggest that hairy root cultures of could be considered for the rational production of valuable compounds by the modification of secondary metabolism.

摘要

是一种木通科木通属的木质藤本植物,在中国传统草药中被广泛应用,且仅分布于满洲生物地理省。由于该植物数量稀少且生长缓慢,因此可以探索其有价值化合物的替代来源。在此,我们通过转化根癌土壤杆菌的 和 基因,建立了 的发根培养物。在转基因细胞培养物中,氮素次生代谢物的积累显著增加。具体而言,在干重基础上,厚朴碱的产量达到了 5.72mg/g,是对照愈伤组织的 5.8 倍,是野生藤本植物的 1.7 倍。同时,负责 物种毒性的马兜铃酸 I 和 II 的含量降低了 10 倍以上。因此,发根提取物对人神经胶质瘤细胞(U-87 MG)、宫颈癌细胞(HeLa CCL-2)和结肠癌细胞(RKO)表现出明显的细胞毒性,但对三阴性乳腺癌细胞(MDA-MB-231)没有明显的活性。我们的研究结果表明,通过对次生代谢物的修饰, 的发根培养物可用于合理生产有价值的化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66e6/10379662/9777a0e2cbac/ijms-24-11240-g001.jpg

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