Liver, colon cancer cells thwarted by compounds derived from hops
The plant that adds flavor, color and bitterness to beer also
produces a primary compound that thwarts cancer cells, and two important
derivatives of the compound do as well, new research at Oregon State University
shows. Unlike the primary compound, xanthohumol, known as XN, the derivatives
don't metabolize into phytoestrogens. Phytoestrogens are plant-based chemicals
similar to female sex hormones that help some types of tumors grow and can
cause other health problems as well.
The
research showed, for the first time, that the derivatives have cancer-fighting
effectiveness similar to that of XN in liver and colon carcinomas. That means
the two non-estrogenic derivatives are attractive alternatives for testing, along
with XN, in future preclinical studies.
The
study was published in the International Journal of Molecular Sciences.
Xanthohumol
is produced by humulus lupulus, the common hop plant. More than 20 years ago,
researchers discovered that XN inhibits cell growth in a variety of cancer cell
lines.
"But
a potential problem with XN is that enzymes in the liver and the gut microbiota
metabolize it into 8- prenylnaringenin, or 8-PN, the most potent phytoestrogen
known," said the study's corresponding author, Adrian Gombart, professor
of biochemistry and biophysics in the College of Science at Oregon State
University and principal investigator at OSU's Linus Pauling Institute.
The
derivatives that don't metabolize into 8-PN are DXN, short for
dihydroxanthohumol, and TXN, which refers to tetrahydroxanthohumol.
Earlier,
Gombart's Linus Pauling Institute colleague and co-author Fred Stevens led a
study into DXN and TXN's effects on metabolic syndrome.
"In
that previous research we showed that the two derivatives reduced weight gain
and improved biomarkers of metabolic syndrome," Gombart said. "XN had
been shown to inhibit proliferation of a variety of cancer cell lines, and in
this study, we demonstrated XN's ability to halt cell growth and kill two liver
cancer cell lines and two colon cancer cell lines. We tested liver and colon
cancer cell lines because oral consumption of XN and its derivatives can lead
to high concentrations in the gut and liver."
Colorectal
cancer is the third most common cause of cancer-related death in the United
States, and liver cancer ranks fifth. The incidence of liver cancer, though,
has tripled in the last four decades.
"For
both of those cancers, discovering new compounds for prevention and treatment
is imperative," Gombart said. "In all the cell lines tested, DXN and
TXN inhibited cell growth and caused cell death, as did XN. And for most cell
types, DXN and TXN were slightly more potent."
Isabelle
E Logan, Cristobal L Miranda, Malcolm B Lowry, Claudia S Maier, Jan F Stevens,
Adrian F Gombart. Antiproliferative and Cytotoxic Activity of Xanthohumol and
Its Non-Estrogenic Derivatives in Colon and Hepatocellular Carcinoma Cell
Lines.
Int. J.
Mol. Sci. 2019, 20(5), 1203. doi: 10.3390/ijms20051203.
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