TitleAntiproliferative and Cytotoxic Activity of Xanthohumol and Its Non-Estrogenic Derivatives in Colon and Hepatocellular Carcinoma Cell Lines.
Publication TypeJournal Article
Year of Publication2019
AuthorsLogan IE, Miranda CL, Lowry MB, Maier CS, Stevens JF, Gombart AF
JournalInt J Mol Sci
Date Published2019 Mar 09

Xanthohumol (XN), a prenylated flavonoid found in hops, inhibits growth in a variety of cancer cell lines; however, its use raises concerns as gut microbiota and the host's hepatic cytochrome P450 enzymes metabolize it into the most potent phytoestrogen known, 8-prenylnaringenin (8-PN). The XN derivatives dihydroxanthohumol (DXN) and tetrahydroxanthohumol (TXN) are not metabolized into 8-PN and they show higher tissue concentrations in vivo compared with XN when orally administered to mice at the same dose. Here we show that DXN and TXN possess improved anti-proliferative activity compared with XN in two colon (HCT116, HT29) and two hepatocellular (HepG2, Huh7) carcinoma cell lines, as indicated by their respective IC values. Furthermore, XN, DXN, and TXN induce extensive apoptosis in all these carcinoma cell lines. Finally, TXN induces G₀/G₁ cell cycle arrest in the colon carcinoma cell line HT29. Our findings suggest that DXN and TXN could show promise as therapeutic agents against colorectal and liver cancer in preclinical studies without the drawback of metabolism into a phytoestrogen.

Alternate JournalInt J Mol Sci
PubMed ID30857300
PubMed Central IDPMC6429097
Grant List5R01AT009168 / / National Institutes of Health /
Department of Biochemistry and Biophysics, OSU / / Christopher and Catherine Mathews Graduate Fellowship /
Oregon Office of Student Access and Completion / / Franz Stenzel M.D. and Kathryn Stenzel II Scholarship /
Linus Pauling Institute, OSU / / 2019 Audrey & George Varsevelt Linus Pauling Institute Graduate Fellowship /
N/A / / OSU Foundation Buhler-Wang Research Fund /