Int. J. Mol. Sci. 2019, 20(5), 1203; https://doi.org/10.3390/ijms20051203
Antiproliferative and Cytotoxic Activity of Xanthohumol and Its Non-Estrogenic Derivatives in Colon and Hepatocellular Carcinoma Cell Lines
Isabelle E. Logan 1
, Cristobal L. Miranda 2, Malcolm B. Lowry 3, Claudia S. Maier 4, Jan F. Stevens 2 and Adrian F. Gombart 5,*
, Cristobal L. Miranda 2, Malcolm B. Lowry 3, Claudia S. Maier 4, Jan F. Stevens 2 and Adrian F. Gombart 5,*
1
Department of Biochemistry and Biophysics, Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA
2
Department of Pharmaceutical Sciences, Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA
3
Department of Microbiology, Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA
4
Department of Chemistry, Oregon State University, Corvallis, OR 97331, USA
5
Linus Pauling Institute, Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, USA
*
Author to whom correspondence should be addressed.
Received: 5 February 2019 / Revised: 28 February 2019 / Accepted: 5 March 2019 / Published: 9 March 2019
(This article belongs to the Special Issue Bioactive Phytochemicals for Cancer Prevention and Treatment)
Abstract
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 IC50 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. View Full-TextKeywords:
xanthohumol; polyphenol; flavonoid; apoptosis; colon cancer; dihydroxanthohumol; tetrahydroxanthohumol; cell cycle; phytochemical; chemoprevention; dietary agent
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Logan, I.E.; Miranda, C.L.; Lowry, M.B.; Maier, C.S.; Stevens, J.F.; Gombart, A.F. Antiproliferative and Cytotoxic Activity of Xanthohumol and Its Non-Estrogenic Derivatives in Colon and Hepatocellular Carcinoma Cell Lines. Int. J. Mol. Sci. 2019, 20, 1203.
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