Methylgerambullin derived from plant Glyccsmis pentaphylla (Retz) correa. Mediates anti-hepatocellular carcinoma cancer effect by activating mitochondrial and endoplasmic reticulum stress signaling and inhibiting AKT and STAT3 pathways.
Food Chem Toxicol
; 149: 112031, 2021 Mar.
Article
em En
| MEDLINE
| ID: mdl-33529679
Hepatocellular carcinoma (HCC) is one of the most common fatal malignant tumors. Glycosmis pentaphylla is used by traditional medical practitioners worldwide to treat various diseases. We isolated and identified a chemical component with potential anti-hepatocellular carcinoma (HCC) effects. Methylgerambullin is a sulfur containing amine and has significant antihepatoma activity in vitro and in vivo. Methylgerambullin was significantly cytotoxic to HCC cells and induces apoptosis in HCC cells. In addition, methylgerambullin is able to inhibit the growth of transplanted tumors in nude mice without significant toxicity. Regarding the anti-cancer mechanism of methylgerambullin, treatment with methylgerambullin increased the expression of caspase-3, caspase-9 and Bax in vitro and in vivo and reduce the expression of B-cell lymphoma-2 (Bcl-2). Simultaneously, methylgerambullin can also affect ERS-related proteins, inhibit Protein Kinase B (Akt) activity, cause dephosphorylation of downstream Bad, and inhibit the expression of the Signal Transducer and Activator of Transcription 3 (STAT3) protein to inhibit HCC cells proliferation. Overall, these results suggest that methylgerambullin can inhibit HCC cells proliferation by inducing mitochondrial apoptosis, activating ERS signaling pathways and inhibiting the Akt and STAT3 pathways.
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MEDLINE
Assunto principal:
Compostos de Enxofre
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Carcinoma Hepatocelular
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Rutaceae
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Amidas
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Neoplasias Hepáticas
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Antineoplásicos Fitogênicos
Tipo de estudo:
Clinical_trials
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article