Highly Cancer Selective Antiproliferative Activity of Natural Prenylated Flavonoids.

Agnieszka Bartmańska,Jarosław Popłoński,Beata Filip-Psurska,Magdalena Milczarek,Tomasz Tronina,Joanna Wietrzyk

doi:10.3390/molecules23112922

Abstract

Xanthohumol (XN) and four minor hops prenylflavonoids: α,β-dihydroxanthohumol (2HXN), isoxanthohumol (IXN), 8-prenylnaringenin (8PN), and 6-prenylnaringenin (6PN), were tested for antiproliferative activity towards human cancer and normal cell lines. Nonprenylated naringenin (NG) was used as a model compound. Xanthohumol, α,β-dihydroxanthohumol and 6-prenylnaringenin were the most active compounds. Xanthohumol exhibited higher antiproliferative activity than cisplatin (CP) against five cancer cell lines: ovarian resistant to cisplatin A2780cis, breast MDA-MB-231 and T-47D, prostate PC-3, and colon HT-29. Isoxanthohumol was more potent than cisplatin against breast cancer cell lines MDA-MB-231 and T-47D whereas 6-prenylnaringenin was stronger than cisplatin against breast cancer cell line T-47D. It was found that tested chalcones possessed highly selective antiproliferative activity towards all tested breast cancer lines compared to the normal breast MCF 10A cell line (the calculated selectivity index ranged from 5 to 10). Low antiproliferative activity of naringenin indicates the importance of the prenyl group with respect to antiproliferative activity.

Highlights

Hop cones are a rich source of prenylated flavonoids
Other prenylated flavonoids occurred at 10–100 fold lower concentrations than xanthohumol and, they were studied less intensely with the exception of 8-prenylnaringenin (8PN)—the most potent phytoestrogen so far known [4]
Xanthohumol is the major flavonoid found in hops, during wort boiling it undergoes thermal isomerisation to isoxanthohumol (IXN), which becomes the major hop flavonoid in beer

Summary

Introduction

Hop cones (hops) are a rich source of prenylated flavonoids. The major flavonoid found in hops with 0.1–1% of dry weight is xanthohumol (XN), the chalcone with a very broad spectrum of biological activities, such as antioxidant, anti-inflammatory and anticancer ones, suggesting a potential chemo-preventive effect [1,2,3].Other prenylated flavonoids occurred at 10–100 fold lower concentrations than xanthohumol and, they were studied less intensely with the exception of 8-prenylnaringenin (8PN)—the most potent phytoestrogen so far known [4]. xanthohumol is the major flavonoid found in hops, during wort boiling it undergoes thermal isomerisation to isoxanthohumol (IXN), which becomes the major hop flavonoid in beer (500 μg/L–3.44 mg/L) [5] and in the human diet. 8-Prenylnaringenin is produced in small amounts in a non-enzymatic way during drying, storage and extraction of hops, and in an enzymatic way along with 6-prenylnaringenin (6PN) from desmethylxanhtohumol during wort boiling.isoxanthohumol is the precursor of 8PN, which can be converted to 8PN by demethylation, catalysed by the cytochrome P-450 enzymes [6] or intestinal microbiota [7]. Hop cones (hops) are a rich source of prenylated flavonoids. The major flavonoid found in hops with 0.1–1% of dry weight is xanthohumol (XN), the chalcone with a very broad spectrum of biological activities, such as antioxidant, anti-inflammatory and anticancer ones, suggesting a potential chemo-preventive effect [1,2,3]. Xanthohumol is the major flavonoid found in hops, during wort boiling it undergoes thermal isomerisation to isoxanthohumol (IXN), which becomes the major hop flavonoid in beer (500 μg/L–3.44 mg/L) [5] and in the human diet. 8-Prenylnaringenin is produced in small amounts in a non-enzymatic way during drying, storage and extraction of hops, and in an enzymatic way along with 6-prenylnaringenin (6PN) from desmethylxanhtohumol during wort boiling.

Methods

Results

Conclusion