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

• Published in: Cancer science 2018-08, Vol.109 (8), p.2576-2589
• Main Authors: He, Qin, Liu, Wenping, Sha, Sha, Fan, Shanshan, Yu, Yajing, Chen, Li, Dong, Ming
• Format: Article
• Language: English
• Subjects: Adenosine Monophosphate - metabolism; AMP; Antineoplastic Agents, Phytogenic - pharmacology; Antitumor activity; Apoptosis; Autophagy; Autophagy - drug effects; Beclin-1 - metabolism; Cancer therapies; Cell adhesion & migration; Cell Line, Tumor; Digital cameras; Fibroblasts; flavokawain B; Flavonoids - pharmacology; Humans; Kinases; Laboratory animals; Lymphocytes B; Metabolism; Mitochondria; Morphology; Original; Phagocytosis; Protein kinase; Proteins; Studies; Thyroid cancer; Thyroid Gland - drug effects; Thyroid Gland - metabolism; Thyroid Neoplasms - drug therapy; Thyroid Neoplasms - metabolism; TOR protein; TOR Serine-Threonine Kinases - metabolism; Up-Regulation - drug effects
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.13699

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. 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 and 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.