Bioactivity-guided isolation of cytotoxic secondary metabolites from the roots of Glycyrrhiza glabra and elucidation of their mechanisms of action

Date

2018-11-15

Author

Cevik, Dicle
Yilmazgoz, S. Burcin
KAN, YÜKSEL
Guzelcan, Ece Akhan
Durmaz, Irem
Atalay, Rengül
KIRMIZIBEKMEZ, HASAN

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

206
views

0
downloads

Licorice (Glycyrrhiza glabra L.) is one of the most widely used plants worldwide for its various pharmacological activities. The aim of this study was to isolate the potential cytotoxic secondary metabolites from the MeOH extract prepared from the roots of Glycyrrhiza glabra through bioactivity-guided isolation procedure and to elucidate their mechanisms of action. The crude MeOH extract as well as CHCl3 and EtOAc subextracts significantly inhibited cell proliferation on hepatocelullar (Huh7), breast (MCF7) and colorectal (HCT116) cancer cell lines with IC50 values in the range of 5.6 to 33.6 mu g/mL. Chromatographic seperations of the CHCl3 and EtOAc subextracts yielded 13 secondary metabolites. Structures were characterized based on NMR and MS data. Amongst isolates, glabridin (1), 4'-O-methylglabridin (2), beta-amyrin (3), kanzonol U (4), glabrene (7) and tet-rahydroxymethoxychalcone (10) were established to be responsible for in vitro cytotoxicity of G. glabra, exerting the best activity particularly against Huh7 cells. Further mechanistic studies demonstrated that 2 and 7 induced caspase-dependent apoptosis by increasing cytochrome C release and subsequently cleaved caspase-9 level in Huh7 cells. Moreover, both compounds decreased pRb and p21 levels and thus induced the accumulation of Huh-7 cells in subG(1) and G(2)/M phases. Compound 10 which displayed the most potent activity in Hoechst staining and cell cycle assays through G(2)/M arrest, caused cell death by apoptosis in Huh7 cells.

Subject Keywords

Agronomy and Crop Science

URI

https://hdl.handle.net/11511/63032

Journal

INDUSTRIAL CROPS AND PRODUCTS

DOI

https://doi.org/10.1016/j.indcrop.2018.08.014

Collections

Graduate School of Informatics, Article

Suggestions

OpenMETU
Core

Micromeria myrtifolia: The influence of the extracting solvents on phenolic composition and biological activity Sarikurkcu, Cengiz; Hanine, Hafida; Sarikurkcu, Rabia Busra; Sarikurkcu, Rifat Tayyib; Amarowicz, Ryszard (Elsevier BV, 2020-03-01) Currently, there is much interest in using the active compounds that exist in plants as natural treatments. The pharmaceutical industry is also looking for novel chemical compounds from natural sources that do not have side effects. The purpose of this study was to identify the antioxidant and enzymatic inhibition activities of different extracts (ethyl acetate, methanol and water) of Micromeria myrtifolia from Turkey. The phenolic constituents in the extracts were also identified using liquid chromatograph...
Ionic liquid pretreatment allows utilization of high substrate loadings in enzymatic hydrolysis of biomass to produce ethanol from cotton stalks Haykir, Nazife Isik; Bakir, Ufuk (Elsevier BV, 2013-11-01) To enhance the enzymatic conversion of cotton stalks to glucose at high substrate loadings and subsequently to produce ethanol, biomass was subjected to ionic liquid and alkaline pretreatments. Ionic liquid, 1-ethyl-3-methylimidazolium acetate (EMIMAc), which reduced biomass crystallinity, was effective in improving the conversion of cotton stalks to glucose (82-85%) regardless of the substrate loading used during enzymatic hydrolysis. On the other hand, the glucose yield decreased from 67% to 55% with an i...
A comparative study on the phenolic composition, antioxidant and enzyme inhibition activities of two endemic Onosma species Saravanakumar, Kandasamy; Sarikurkcu, Cengiz; Sarikurkcu, Rifat Tayyib; Wang, Myeong-Hyeon (Elsevier BV, 2019-12-15) The studies on bioactivities of plant extracts are a fundamental requirement for future pharmacological research. Therefore, the present study extracted the phytochemicals from the two endemic species such as Onosma isaurica and O. bracteosa and tested their antioxidant, reducing power and enzyme inhibitory activities followed by scanning of the phytochemicals in the extracts by using liquid chromatography-electrospray tandem mass spectrometry (LC-ESI-MS/MS). The results revealed that the antioxidant activi...
Agrobacterium tumefaciens-mediated genetic transformation of a recalcitrant grain legume, lentil (Lens culinaris Medik) Akcay, Ufuk Celikkol; Mahmoudian, M.; Kamci, H.; YÜCEL, MUSTAFA; Öktem, Hüseyin Avni (Springer Science and Business Media LLC, 2009-03-01) A simple and reproducible Agrobacterium-mediated transformation protocol for a recalcitrant legume plant, lentil (Lens culinaris M.) is reported. Application of wounding treatments and efficiencies of three Agrobacterium tumefaciens strains, EHA105, C58C1, and KYRT1 were compared for T-DNA delivery into lentil cotyledonary node tissues. KYRT1 was found to be on average 2.8-fold more efficient than both EHA105 and C58C1 for producing transient beta-glucuronidase (GUS) gene (gus) expression on cotyledonary pe...
Identification and characterization of hydrolytic enzymes from the midgut of Sunn Pest of wheat (Eurygaster integriceps) Ogur, E.; YÜCEL, MUSTAFA; Öktem, Hüseyin Avni (Informa UK Limited, 2009-01-01) To help in the development of Sunn Pest-resistant transgenic plants employing protease or alpha-amylase inhibitors, midgut hydrolytic enzymes of Sunn Pest (Eurygaster integriceps, Put.) (Heteroptera: Scutelleridae) were identified and characterized biochemically. We observed levels of very low proteolytic activity of trypsin (3 nmoles/min/mg), elastase (0.66 nmoles/min/mg) and leucine aminopeptidase-like (14.4 nmoles/min/mg) proteases, but no chymotrypsin and papain-like activity. Proteolytic activities wer...

Citation Formats

D. Cevik et al., “Bioactivity-guided isolation of cytotoxic secondary metabolites from the roots of Glycyrrhiza glabra and elucidation of their mechanisms of action,” INDUSTRIAL CROPS AND PRODUCTS, pp. 389–396, 2018, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/63032.