Open AccessAdenosine 5'‐monophosphate‐activated protein kinase‐dependent mTOR pathway is involved in flavokawain B‐induced autophagy in thyroid cancer cells
Author(s) -
He Qin,
Liu Wenping,
Sha Sha,
Fan Shanshan,
Yu Yajing,
Chen Li,
Dong Ming
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13699
Subject(s) - autophagy , pi3k/akt/mtor pathway , cancer cell , chalcone , protein kinase a , chemistry , kinase , thyroid cancer , downregulation and upregulation , mechanism of action , microbiology and biotechnology , cancer research , biochemistry , cancer , biology , in vitro , signal transduction , thyroid , apoptosis , endocrinology , stereochemistry , genetics , gene
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.