Suyanee Thongchot 1 2 3 , Malinee Thanee 1 3 , Watcharin Loilome 1 3 , Anchalee Techasen 3 4 , Thidarat Boonmars 3 5 , Prakasit Sa-Ngiamwibool 3 6 , Attapol Titapun 3 7 , Puangrat Yongvanit 3 , Ciro Isidoro 2 , Nisana Namwat 1 3
Affiliations
1 Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 123 Mitraparp Highway, Khon Kaen, 40002, Thailand.
2 Laboratory of Molecular Pathology, Department of Health Sciences, Università del Piemonte Orientale “A. Avogadro”, Via Solaroli 17, 28100, Novara, Italy.
3 Cholangiocarcinoma Research Institute, Khon Kaen University, 123 Mitraparp Highway, Khon Kaen, 40002, Thailand.
4 Faculty of Associated Medical Sciences, Khon Kaen University, 123 Mitraparp Highway, Khon Kaen, 40002, Thailand.
5 Department of Parasitology, Faculty of Medicine, Khon Kaen University, 123 Mitraparp Highway, Khon Kaen, 40002, Thailand.
6 Department of Pathology, Faculty of Medicine, Khon Kaen University, 123 Mitraparp Highway, Khon Kaen, 40002, Thailand.
7 Department of Surgery, Faculty of Medicine, Khon Kaen University, 123 Mitraparp Highway, Khon Kaen, 40002, Thailand.
PMID: 32670817
PMCID: PMC7340870
DOI: 10.1016/j.jtcme.2019.02.001
J Tradit Complement Med. 2019 Feb 10;10(3):230-235. doi: 10.1016/j.jtcme.2019.02.001. eCollection 2020 May.
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.
Keywords: Apoptosis; BECLIN1; CCA, cholangiocarcinoma; CIQ, chloroquine; Cancer; Cholangiocarcinoma; Flavonoids; Herbal medicine; LC3; NDMA, N-dinitrosomethylamine; OV, Opisthorchis viverrini; Opistorchis viverrini; SP-1, Spautin-1; Spautin; Therapy; XH, Xanthohumol.
