Xanthohumol inhibits STAT3 activation pathway leading to growth suppression and apoptosis induction in human cholangiocarcinoma cells

Dokduang,Hasaya; Yongvanit,Puangrat; Namwat,Nisana; Pairojkul,Chawalit; Sangkhamanon,Sakkarn; Yageta,Mika  Sakurai; Murakami,Yoshinori; Loilome,Watcharin

doi:10.3892/or.2016.4584

Xanthohumol inhibits STAT3 activation pathway leading to growth suppression and apoptosis induction in human cholangiocarcinoma cells

Authors:
- Hasaya Dokduang
- Puangrat Yongvanit
- Nisana Namwat
- Chawalit Pairojkul
- Sakkarn Sangkhamanon
- Mika Sakurai Yageta
- Yoshinori Murakami
- Watcharin Loilome
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Affiliations: Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand, Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand, Division of Molecular Pathology, Department of Cancer Biology, Institute of Medical Science, the University of Tokyo, Tokyo 108-8639, Japan
Published online on: January 21, 2016 https://doi.org/10.3892/or.2016.4584
Pages: 2065-2072

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Abstract

STAT3 plays a significant role in the development of cholangiocarcinoma (CCA) associated with the liver fluke (Opisthorchis viverrini; Ov). Xanthohumol (XN), a prenylated flavonoid extracted from hops, has known anticancer activity and could potentially target STAT3. The present study determined the effect of XN on STAT3, as well as ascertained its usefulness against CCA. The CCA cell proliferation at 20 µM and 50 µM of XN was shown to inhibited, while 20 µM partially inhibited IL-6-induced STAT3 activation. At 50 µM, the inhibition was complete. The reduction in STAT3 activity at 20 and 50 µM was associated with a significant reduction of CCA cell growth and apoptosis. We also found that the administration of 50 µM XN orally in drinking water to nude mice inoculated with CCA led to a reduction in tumor growth in comparison with controls. In addition, apoptosis of cancer cells increased although there was no visible toxicity. The present study shows that XN can inhibit STAT3 activation both in vivo and in vitro due to suppression of the Akt-NFκB signaling pathway. XN should be considered as a possible therapeutic agent against CCA.

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