Curative effect of xanthohumol supplementation during liver fluke-associated cholangiocarcinogenesis: Potential involvement of autophagy

Journal of Traditional and Complementary Medicine
Suyanee ThongchotNisana Namwat

Abstract

Xanthohumol (XH), a plant flavonoid, was shown to attenuate cholangiocarcinoma (CCA) development induced by the liver fluke Opisthorchis viverrini (Ov) and N-dinitrosomethylamine (NDMA) in the hamster model. We investigated the possible involvement of autophagy, a self-degrading process dysregulated in cancer, in XH chemotherapeutic effect. During cholangiocarcinogenesis, the expression of LC3 (an autophagic marker) was increased in the precancerous stage and decreased in the cancerous stage. The XH-treated ON (Ov plus NDMA) group showed retarded progression of CCA along with increased expression of LC3. The possible relation between autophagy and cell death was investigated in cultured human CCA cells. XH induced apoptosis associated with reduced expression of BCL-2 and increased expression of BAX. In parallel, XH induced the autophagy flux, as testified by increased LC3-II and decreased p62, along with induction of BECLIN1 and Vps34. Inhibition of BECLIN1-dependent autophagy greatly limited XH toxicity in CCA cells. These data suggest that XH attenuates the development of CCA through overstimulation of autophagy which then precipitates apoptosis.

Citations

Aug 14, 2020·International Journal of Molecular Sciences·Rittibet YapasertRatana Banjerdpongchai
May 1, 2021·International Journal of Molecular Sciences·Vancha HarishAnupam Bishayee
Jul 2, 2021·Journal of Traditional and Complementary Medicine·Kesara Na-BangchangJuntra Karbwang
Jul 23, 2021·Expert Opinion on Investigational Drugs·Watcharin LoilomeSureerat Padthaisong

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Methods Mentioned

BETA
xenograft
electrophoresis
flow cytometry

Software Mentioned

Carl
ImageJ
Zeiss ZEN
CellCounter
SPSS

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