Synergistic anticancer effects of combined γ-tocotrienol and oridonin treatment is associated with the induction of autophagy.
Mol Cell Biochem
; 408(1-2): 123-37, 2015 Oct.
Article
em En
| MEDLINE
| ID: mdl-26112904
γ-Tocotrienol and oridonin are natural phytochemicals that display potent anticancer activity. Studies showed that combined treatment with subeffective doses of γ-tocotrienol with oridonin resulted in synergistic autophagic and apoptotic effects in malignant +SA, but not normal CL-S1 mouse mammary epithelial cells in vitro. Specifically, combined treatment with low doses of γ-tocotrienol (8 µM) and oridonin (2 µM) for 24 h resulted in synergistic inhibition of +SA mammary cancer cells viability. This combination significantly enhanced the expression of autophagy cellular markers including the conversion of LC3B-I to LC3B-II, beclin-1, Atg3, Atg7, Atg5-Atg12, LAMP-1 and cathepsin-D, and pretreatment with the autophagy inhibitors 3-methyladenine (3-MA) or bafilomycin A1 (Baf1) blocked these effects. Furthermore, blockade of γ-tocotrienol and oridonin-induced autophagy with 3-MA or Baf1 induced a modest, but significant reduction in cytotoxicity resulting from the combined treatment of these phytochemicals. The anticancer effects of combination treatment was also associated with a large suppression in Akt/mTOR mitogenic signaling and corresponding increase in the levels of apoptotic cellular marker including cleaved caspase-3 and PARP, and Bax/Bcl-2 ratio in these tumor cells. These effects were also found to be selective against cancer cells, since similar combined treatment with γ-tocotrienol and oridonin did not induce autophagy or reduce viability of normal mouse CL-S1 mammary epithelial cells. These findings indicate that combined γ-tocotrienol and oridonin-induced autophagy plays a role in mediating the synergistic anticancer effects of these phytochemicals.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vitamina E
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Neoplasias da Mama
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Cromanos
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Diterpenos do Tipo Caurano
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Antineoplásicos Fitogênicos
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Mol Cell Biochem
Ano de publicação:
2015
Tipo de documento:
Article