Novel histone deacetylase inhibitors derived from Magnolia officinalis significantly enhance TRAIL-induced apoptosis in non-small cell lung cancer.
Pharmacol Res
; 111: 113-125, 2016 09.
Article
en En
| MEDLINE
| ID: mdl-27268146
ABSTRACT
Histone modifications play critical roles in the progression of non-small cell lung cancer (NSCLC), which accounts for almost 85% of all diagnosed lung cancers. Magnolol and polyphenol mixture (PM) derived from Magnolia officinalis exhibited remarkable antitumor activities in lung cancer. However, the epigenetic effects and molecular mechanisms of magnolol and PM in NSCLC have yet to be reported. In this study, the epigenetic effects of magnolol and PM in NSCLC were examined in vitro and in vivo. Results revealed that magnolol and PM significantly suppressed the expression levels and function of class I histone deacetylases (HDACs). In A549 and H1299 cells, magnolol and PM remarkably induced cell apoptosis by arresting the cell cycle in the G0/G1 phase while simultaneously activating various pro-apoptotic signals, including TRAIL-R2 (DR5), Bax, caspase 3, cleaved caspase 3, and cleaved PARP. However, these apoptosis-promoting effects could be attenuated by TSA, which is a specific class I HDACs inhibitor. ChIP assays also demonstrated that magnolol and PM significantly enriched the histone acetyl mark (H3K27ac) in the promoter region of DR5. In A549 xenograft model, magnolol and PM notably reduced tumor growth by 44.40% and 35.40%, respectively. Therefore, magnolol and PM, as potential inhibitors of class I HDACs, induced tumor cell apoptosis and suppressed tumor growth partially by epigenetically activating DR5, which is a key protein in death receptor signaling pathway.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Métodos Terapéuticos y Terapias MTCI:
Terapias_biologicas
/
Aromoterapia
/
Plantas_medicinales
Asunto principal:
Extractos Vegetales
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Apoptosis
/
Carcinoma de Pulmón de Células no Pequeñas
/
Magnolia
/
Ligando Inductor de Apoptosis Relacionado con TNF
/
Histona Desacetilasa 1
/
Inhibidores de Histona Desacetilasas
/
Neoplasias Pulmonares
/
Antineoplásicos Fitogénicos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Pharmacol Res
Año:
2016
Tipo del documento:
Article
País de afiliación:
China