NF-κB inhibitory and cytotoxic activities of hexacyclic triterpene acid constituents from Glechoma longituba.
Phytomedicine
; 63: 153037, 2019 Oct.
Article
em En
| MEDLINE
| ID: mdl-31357075
ABSTRACT
BACKGROUND:
Non-Small-Cell Lung Cancer (NSCLC) is the most-frequent cause of cancer death, and novel chemotherapeutic drugs for treating NSCLC are urgently needed. 2α, 3α, 23-trihydroxy-13α, 27-cyclours-11-en-28-oic acid (euscaphic acid G) is a new hexacyclic triterpene acid isolated by our group from Glechoma longituba (Nakai) Kupr. However, the underlying mechanisms responsible for the anticancer effects of hexacyclic triterpene acid have not been elucidated.PURPOSE:
In the present work, we evaluated growth inhibitory effect of the new isolated hexacyclic triterpene acid and explored the underlying molecular mechanisms. METHODS/STUDY DESIGNS Herbs were extracted and constituents were purified by chromatographic separation, including silica gel, ODS, MCI, Sephadex LH-20 and preparative HPLC. The compound structures were elucidated by the use of UV, NMR and MS spectral data. The anticancer activity of euscaphic acid G was evaluated by MTT assay. Cell cycle, apoptosis, reactive oxygen species and mitochondrial membrane potential were determined by flow cytometry. To display the possible mechanism of euscaphic acid G on NCI-H460 cells, RT-PCR, immunofluorescence and Western blot analysis were carried out.RESULTS:
A new hexacyclic triterpene acid, euscaphic acid G, together with fifteen known triterpenoids, was isolated from the aerial parts of G. longituba. Our results showed that euscaphic acid G exerted strong anti-proliferative activity against NCI-H460 cells in a concentration- and time-dependent manner. Flow cytometry demonstrated euscaphic acid G arrested the cell cycle at G1 phase, induced cellular apoptosis, accompanied by ROS generation and mitochondrial membrane potential reduction. Mechanistic studies revealed that euscaphic acid G treatment inhibited IKKα/ß phosphorylation and IκBα phosphorylation, which subsequently caused the blockage of NF-κB p65 phosphorylation and nuclear translocation.CONCLUSION:
In conclusion, these results suggested that euscaphic acid G from G. longituba showed potential anticancer effects against lung cancer cells via inducing cell cycle arrest and apoptosis, at least partly, through NF-κB signaling pathways.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Triterpenos
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NF-kappa B
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Lamiaceae
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Antineoplásicos Fitogênicos
Limite:
Humans
Idioma:
En
Revista:
Phytomedicine
Assunto da revista:
TERAPIAS COMPLEMENTARES
Ano de publicação:
2019
Tipo de documento:
Article