Xanthohumol from Humulus lupulus L. induces glioma cell autophagy via inhibiting Akt/mTOR/S6K pathway

Wan-Jung Lu, Chao Chien Chang, Li Ming Lien, Ting Lin Yen, Hou Chang Chiu, Shih Yi Huang, Joen Rong Sheu, Kuan Hung Lin

研究成果: 雜誌貢獻文章

7 引文 斯高帕斯(Scopus)

摘要

Xanthohumol is the major prenylated flavonoid in the hop plant (Humulus lupulus L.). The aim of our study was to determine the effects of xanthohumol on the U87 glioma cell line. In the present study, the U87 glioma cell line was treated with xanthohumol. Our results showed that xanthohumol reduced cell viability and induced apoptosis detected by the MTT assay and PI-Annexin V doubling staining, respectively, in glioma cells. In the acridine orange staining experiments, we also found that xanthohumol induced autophagy, as detected by flow cytometry and confocal microscopy. Western blot also showed that xanthohumol inhibited the Akt/mTOR/S6K pathway and promoted LC3-II formation and p62 degradation. Moreover, we found that the Erk inhibitor or JNK inhibitor could partially reversed the xanthohumol-induced LC3-II formation and cell death. Otherwise, autophagy inhibition by bafilomycin A1, Atg5 shRNA, or Atg7 shRNA partially protected xanthohumol-induced cell death. These findings indicated that xanthohumol may induce glioma cell death through induction of autophagy. In addition, we also demonstrated that xanthohumol inhibited tumour growth in a mouse xenograft model. In conclusion, xanthohumol may induce autophagy in glioma cells through both Akt/mTOR/S6K pathway and MAPK cascade and inhibit tumour growth in vivo. Our findings also support that autophagy induction may provide benefits to increasing therapeutic efficacy of anti-cancer drugs for the treatment of glioblastoma multiforme.
原文英語
文章編號1255
頁(從 - 到)538-549
頁數12
期刊Journal of Functional Foods
18
DOIs
出版狀態已發佈 - 十月 1 2015

ASJC Scopus subject areas

  • Food Science
  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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