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

Cancer Sci. 2018 Aug;109(8):2576-2589. doi: 10.1111/cas.13699. Epub 2018 Jul 20.


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.

Keywords: apoptosis; autophagy; flavokawain B; metabolism; thyroid cancer.

MeSH terms

  • Adenosine Monophosphate / metabolism*
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Autophagy / drug effects*
  • Beclin-1 / metabolism
  • Cell Line, Tumor
  • Flavonoids / pharmacology*
  • Humans
  • TOR Serine-Threonine Kinases / metabolism*
  • Thyroid Gland / drug effects
  • Thyroid Gland / metabolism
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / metabolism
  • Up-Regulation / drug effects


  • Antineoplastic Agents, Phytogenic
  • Beclin-1
  • Flavonoids
  • flavokawain B
  • Adenosine Monophosphate
  • MTOR protein, human
  • TOR Serine-Threonine Kinases