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

Industrial Crops and Products · Kasım 2018

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YÖKSİS Kayıtları
Bioactivity-guided isolation of cytotoxic secondary metabolites from the roots of Glycyrrhiza glabra and elucidation of their mechanisms of action
INDUSTRIAL CROPS AND PRODUCTS · 2018 SCI
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Makale Bilgileri

DergiIndustrial Crops and Products
Yayın TarihiKasım 2018
Cilt / Sayfa124 · 389-396
Özet 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 μg/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), β-amyrin (3), kanzonol U (4), glabrene (7) and tetrahydroxymethoxychalcone (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 subG1 and G2/M phases. Compound 10 which displayed the most potent activity in Hoechst staining and cell cycle assays through G2/M arrest, caused cell death by apoptosis in Huh7 cells.

Yazarlar (7)

1
Dicle Çevik
ORCID: 0000-0001-9257-5765
2
Burçin Yılmazgöz
3
Yüksel Kan
4
Ece Akhan Güzelcan
5
Irem Durmaz
6
Rengul Cetin-Atalay
7
Hasan Kırmızıbekmez

Anahtar Kelimeler

Apoptosis Cytotoxic activity Glycyrrhiza glabra Huh7 Liver cancer Secondary metabolites

Kurumlar

Middle East Technical University (METU)
Ankara Turkey
Selçuk Üniversitesi
Selçuklu Turkey
Yeditepe University
Istanbul Turkey

Metrikler

18
Atıf
7
Yazar
6
Anahtar Kelime

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