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

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number1255
Pages (from-to)538-549
Number of pages12
JournalJournal of Functional Foods
Volume18
DOIs
Publication statusPublished - Oct 1 2015

Fingerprint

Humulus lupulus
Humulus
autophagy
Autophagy
Glioma
cell death
cells
cell lines
acridine orange
neoplasms
antineoplastic agents
hops
Cell Death
growth models
drug therapy
cell viability
flow cytometry
Small Interfering RNA
Western blotting
flavonoids

Keywords

  • Autophagy
  • Glioblastoma multiforme
  • MAPK
  • MTOR
  • Xanthohumol

ASJC Scopus subject areas

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

Cite this

Xanthohumol from Humulus lupulus L. induces glioma cell autophagy via inhibiting Akt/mTOR/S6K pathway. / Lu, Wan-Jung; Chang, Chao Chien; Lien, Li Ming; Yen, Ting Lin; Chiu, Hou Chang; Huang, Shih Yi; Sheu, Joen Rong; Lin, Kuan Hung.

In: Journal of Functional Foods, Vol. 18, 1255, 01.10.2015, p. 538-549.

Research output: Contribution to journalArticle

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abstract = "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.",
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