Induction of cytotoxic and genotoxic responses by natural and novel quercetin glycosides

Anya Engen; Junko Maeda; David E Wozniak; Colleen A Brents; Justin J Bell; Mitsuru Uesaka; Yasushi Aizawa; Takamitsu A Kato

doi:10.1016/j.mrgentox.2015.04.007

Induction of cytotoxic and genotoxic responses by natural and novel quercetin glycosides

Mutat Res Genet Toxicol Environ Mutagen. 2015 Jun:784-785:15-22. doi: 10.1016/j.mrgentox.2015.04.007. Epub 2015 Apr 13.

Authors

Anya Engen¹, Junko Maeda¹, David E Wozniak¹, Colleen A Brents¹, Justin J Bell¹, Mitsuru Uesaka², Yasushi Aizawa³, Takamitsu A Kato⁴

Affiliations

¹ Department of Environmental and Radiological Health Sciences, Colorado State University, 1618 Campus Delivery, Fort Collins, CO 80523, USA.
² Graduate School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan.
³ Graduate School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan; Research and Development Group, Toyo Sugar Refining Co., Ltd., Tokyo 103-0046, Japan.
⁴ Department of Environmental and Radiological Health Sciences, Colorado State University, 1618 Campus Delivery, Fort Collins, CO 80523, USA. Electronic address: Takamitsu.Kato@Colostate.edu.

PMID: 26046972
DOI: 10.1016/j.mrgentox.2015.04.007

Abstract

The flavonoids quercetin, and its natural glycosides isoquercetin and rutin, are phytochemicals commonly consumed in plant-derived foods. Semi-synthetic water-soluble isoquercetin and rutin glycosides, maltooligosyl isoquercetin, monoglucosyl rutin and maltooligosyl rutin were developed by synthetic glycosylation to overcome solubility challenges for improved incorporation in food and medicinal applications. Quercetin and its natural glycosides are known to induce genetic instability and decrease cell proliferation. Using a system of Chinese hamster ovary (CHO) cells, this study examined the differences in cytotoxic and genotoxic responses induced by natural and synthetic flavonoids. Bioactivity evaluations using poly(ADP-ribose) polymerase (PARP) ELISA showed that the synthetic flavonoids were less effective in inhibiting PARP than the natural flavonoids, where PARP inhibitory effects decreased with glycosylation of flavonoids. In the genotoxic studies, treatments with flavonoids at a concentration range of 0.2 μM-1 mM induced significant frequencies of sister chromatid exchange (SCE) and micronuclei in CHO cells compared to spontaneous occurrences. The synthetic flavonoids monoglucosyl rutin and maltooligosyl rutin induced less genotoxic effects than the natural flavonoids. However, maltooligosyl isoquercetin induced similar responses as isoquercetin and rutin. The growth inhibition studies showed glycosylation dependent cytotoxicity in natural flavonoids. The quercetin aglycone exhibited the highest toxicity out of all the flavonoids studied. Differences in growth inhibition were not observed between the synthetic flavonoids, maltooligosyl isoquercetin and monoglucosyl rutin, and natural isoquercetin and rutin, respectively. Maltooligosyl rutin induced less cytotoxicity than rutin and monoglucosyl rutin. Our in vitro studies demonstrated that the synthetic flavonoids generally induced less genotoxic responses than their natural counterparts.

Keywords: Flavonoid; Glycoside; Micronuclei; Sister chromatid exchange.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antioxidants / pharmacology*
CHO Cells
Cell Proliferation / drug effects
Cricetinae
Cricetulus
Cytogenetic Analysis / methods
DNA Damage*
Poly(ADP-ribose) Polymerases / metabolism*
Quercetin / analogs & derivatives*
Quercetin / chemistry
Quercetin / pharmacology*
Rutin / chemistry
Rutin / pharmacology
Sister Chromatid Exchange / drug effects

Substances

Antioxidants
isoquercitrin
Rutin
Quercetin
Poly(ADP-ribose) Polymerases