Enhanced Production of Nitrogenated Metabolites with Anticancer Potential in Aristolochia manshuriensis Hairy Root Cultures.
Yuri N ShkrylGalina K TchernodedYulia A YugayValeria P GrigorchukMaria R SorokinaTatiana Yu GorpenchenkoOlesya D KudinovaAnton I DegtyarenkoMaria S OnishchenkoNikita A ShvedVadim V KumeikoVictor P BulgakovPublished in: International journal of molecular sciences (2023)
Aristolochia manshuriensis 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 A. manshuriensis transformed with Agrobacterium rhizogenes root oncogenic loci ( rol)B and rolC 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 Aristolochia 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 A. manshuriensis could be considered for the rational production of valuable A. manshuriensis compounds by the modification of secondary metabolism.
Keyphrases
- cell cycle arrest
- induced apoptosis
- breast cancer cells
- cell death
- ms ms
- endothelial cells
- genome wide
- body mass index
- pi k akt
- physical activity
- signaling pathway
- single cell
- drinking water
- dna methylation
- bone marrow
- risk assessment
- endoplasmic reticulum stress
- gene expression
- weight loss
- cell therapy
- mesenchymal stem cells
- genetic diversity
- genome wide association