Bigelovin, a sesquiterpene lactone, suppresses tumor growth through inducing apoptosis and autophagy via the inhibition of mTOR pathway regulated by ROS generation in liver cancer.
Biochem Biophys Res Commun
; 499(2): 156-163, 2018 05 05.
Article
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| MEDLINE
| ID: mdl-29548826
ABSTRACT
Bigelovin (BigV) is a sesquiterpene lactone, isolated from Inula helianthus aquatica, which has been reported to induce apoptosis and show anti-inflammatory and anti-angiogenic activities. Nevertheless, the effects of BigV on liver cancer and the underlying mechanisms have not been investigated. In the study, we found that BigV exhibited potential anti-tumor activities against human liver cancer in vitro and in vivo. BigV reduced the cell proliferation and colony formation. BigV induced apoptosis through improving the cleavage of Caspase-3 and poly (ADP-ribose) polymerase 1 (PARP-1). The process was along with the activation of autophagy, as proved by the enhanced accumulation of autophagosomes, the microtubule-associated light chain 3B-II (LC3B-II) and Beclin-1, and p62 decrease. Further, the autophagy blockage markedly sensitized BigV-induced cell death, indicating the cytoprotective function of autophagy in liver cancer cell lines. In addition, BigV treatment inactivated the pathway of protein kinase B (AKT)/mammalian target of rapamycin (mTOR)/ribosomal protein S6 kinase (p70S6K). Of note, BigV-induced cell death was abolished by over-expressing the phosphorylation of mTOR. Intriguingly, the induction of apoptosis and autophagy were eliminated by the pretreatment of reactive oxygen species (ROS) scavenger N-acetyl-l-cysteine (NAC), suggesting that ROS played an important role in the regulation of BigV-induced cell death. Finally, in vivo studies demonstrated that BigV significantly suppressed the growth of HepG2 cancer xenograft tumors through the activation of apoptosis and autophagy in a dose-dependent manner with low systemic toxicity. In conclusion, the results revealed that BigV had significant antitumor effects against human liver cancer and it may potentially be used as a novel antitumor agent for the prevention of liver cancer.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Sesquiterpenos
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Autofagia
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Transducción de Señal
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Especies Reactivas de Oxígeno
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Apoptosis
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Serina-Treonina Quinasas TOR
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Lactonas
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Neoplasias Hepáticas
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2018
Tipo del documento:
Article
País de afiliación:
China