ReferenceID 3171

Xanthohumol Inhibits the Growth of Keratin 18-Overexpressed Esophageal Squamous Cell Carcinoma in vitro and in vivo

Front Cell Dev Biol

Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related death worldwide. Xanthohumol is a prenylated flavonoid isolated from hops. Although xanthohumol has been reported to exert anti-obesity, hypo

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Reference Id
3171
Evidence Id
19761
Core Evidence Id
19761
Source Reference Id
6320
Herb2 Reference Id
HBREF007117
Subject Paper Key
HBIN048442_32509787
Pubmed Id
32509787
Doi
10.3389/fcell.2020.00366
Paper Title
Xanthohumol Inhibits the Growth of Keratin 18-Overexpressed Esophageal Squamous Cell Carcinoma in vitro and in vivo
Paper Abstract
Esophageal squamous cell carcinoma (ESCC) is a leading cause of cancer-related death worldwide. Xanthohumol is a prenylated flavonoid isolated from hops. Although xanthohumol has been reported to exert anti-obesity, hypoglycemic, anti-hyperlipidemia and anti-cancer activities, the mechanisms underlying its chemotherapeutic activity are yet to be elucidated. In the present study, we found that xanthohumol inhibited ESCC cell proliferation in vitro and in vivo by targeting keratin (KRT)-18. Xanthohumol suppressed the proliferation, foci formation, and anchorage-independent colony growth of KYSE30 cells. Using xanthohumol-sepharose conjugated bead pull-down and mass/mass analysis, we found that KRT18 is a novel target of xanthohumol in KYSE30 cells. KRT18 protein was highly expressed in patient ESCC tissues compared to adjunct tissues. Anti-proliferative activity of xanthohumol was abrogated or enhanced according to the knockdown or overexpression of KRT18 protein, respectively. Xanthohumol also induced apoptosis and cell cycle arrest at G1 phase which was associated with the modulation of expression of related makers including cyclin D1, cyclin D3, and cleaved-PARP, Bcl-2, cytochrome c and Bax. While xanthohumol attenuated KRT18 protein expression, it failed to cause any change in the KRT18 mRNA level. Furthermore, oral administration of xanthohumol decreased tumor volume and weight in patient-derived xenografts (PDXs) tumors having overexpressed KRT18. Overall these results suggest that xanthohumol acts as a KRT18 regulator to suppress the growth of ESCC.
Journal
Front Cell Dev Biol
Publish Year
2020
Experiment Subject
patient; kyse30 cells
Experiment Type
Animal & Cell Experiment
Phenotype Related
Cancer-related Death; Tumor; Esophageal Squamous Cell Carcinoma; Tumors
Paper Title Cn
Paper Title En
Xanthohumol Inhibits the Growth of Keratin 18-Overexpressed Esophageal Squamous Cell Carcinoma in vitro and in vivo
Bilingual Status
semi_complete