Dataset Information

Adenosine 5'-monophosphate-activated protein kinase-dependent mTOR pathway is involved in flavokawain B-induced autophagy in thyroid cancer cells.

ABSTRACT: Flavokawain B (FKB), a natural kava chalcone, shows potent antitumor activity in various types of cancer, although the mechanism of action remains unclear. In this study, we report that FKB has profound effects on the metabolic state of human thyroid cancer (TCa) cells, leading to high autophagy flux through upregulation of AMP-activated protein kinase, which in turn inhibits mTOR and activates Beclin-1 in TCa cells. We further report that the autophagy induced by FKB plays a prosurvival role in TCa cells both in vitro and in vivo. In conclusion, our findings provide evidence that combination treatment with FKB and pharmacological autophagy inhibitors will be a potential therapeutic strategy for the treatment of TCa.

SUBMITTER: He Q

PROVIDER: S-EPMC6113436 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Adenosine 5'-monophosphate-activated protein kinase-dependent mTOR pathway is involved in flavokawain B-induced autophagy in thyroid cancer cells.

He Qin Q Liu Wenping W Sha Sha S Fan Shanshan S Yu Yajing Y Chen Li L Dong Ming M

Cancer science 20180720 8

Flavokawain B (FKB), a natural kava chalcone, shows potent antitumor activity in various types of cancer, although the mechanism of action remains unclear. In this study, we report that FKB has profound effects on the metabolic state of human thyroid cancer (TCa) cells, leading to high autophagy flux through upregulation of AMP-activated protein kinase, which in turn inhibits mTOR and activates Beclin-1 in TCa cells. We further report that the autophagy induced by FKB plays a prosurvival role in ...[more]

PMID: 29908094

Similar Datasets

Project description:OBJECTIVE:Our goal was to determine the mechanism by which mitochondrial oxidative stress impairs collateral growth in the heart. APPROACH AND RESULTS:Rats were treated with rotenone (mitochondrial complex I inhibitor that increases reactive oxygen species production) or sham-treated with vehicle and subjected to repetitive ischemia protocol for 10 days to induce coronary collateral growth. In control rats, repetitive ischemia increased flow to the collateral-dependent zone; however, rotenone treatment prevented this increase suggesting that mitochondrial oxidative stress compromises coronary collateral growth. In addition, rotenone also attenuated mitochondrial complex I activity and led to excessive mitochondrial aggregation. To further understand the mechanistic pathway(s) involved, human coronary artery endothelial cells were treated with 50 ng/mL vascular endothelial growth factor, 1 µmol/L rotenone, and rotenone/vascular endothelial growth factor for 48 hours. Vascular endothelial growth factor induced robust tube formation; however, rotenone completely inhibited this effect (P<0.05 rotenone versus vascular endothelial growth factor treatment). Inhibition of tube formation by rotenone was also associated with significant increase in mitochondrial superoxide generation. Immunoblot analyses of human coronary artery endothelial cells with rotenone treatment showed significant activation of adenosine monophosphate activated kinase (AMPK)-? and inhibition of mammalian target of rapamycin and p70 ribosomal S6 kinase. Activation of AMPK-? suggested impairments in energy production, which was reflected by decrease in O2 consumption and bioenergetic reserve capacity of cultured cells. Knockdown of AMPK-? (siRNA) also preserved tube formation during rotenone, suggesting the negative effects were mediated by the activation of AMPK-?. Conversely, expression of a constitutively active AMPK-? blocked tube formation. CONCLUSIONS:We conclude that activation of AMPK-? during mitochondrial oxidative stress inhibits mammalian target of rapamycin signaling, which impairs phenotypic switching necessary for the growth of blood vessels.

Dataset Information

Adenosine 5'-monophosphate-activated protein kinase-dependent mTOR pathway is involved in flavokawain B-induced autophagy in thyroid cancer cells.

Publications

Adenosine 5'-monophosphate-activated protein kinase-dependent mTOR pathway is involved in flavokawain B-induced autophagy in thyroid cancer cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets