title: Induction of cytotoxic and genotoxic responses by natural and novel quercetin glycosides.
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.
authors.affiliation: Department of Environmental and Radiological Health Sciences, Colorado State University, 1618 Campus Delivery, Fort Collins, CO 80523, USA.
authors.forename: Anya
authors.initials: A
authors.lastname: Engen
authors.affiliation: Department of Environmental and Radiological Health Sciences, Colorado State University, 1618 Campus Delivery, Fort Collins, CO 80523, USA.
authors.forename: Junko
authors.initials: J
authors.lastname: Maeda
authors.affiliation: Department of Environmental and Radiological Health Sciences, Colorado State University, 1618 Campus Delivery, Fort Collins, CO 80523, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Wozniak
authors.affiliation: Department of Environmental and Radiological Health Sciences, Colorado State University, 1618 Campus Delivery, Fort Collins, CO 80523, USA.
authors.forename: Colleen A
authors.initials: CA
authors.lastname: Brents
authors.affiliation: Department of Environmental and Radiological Health Sciences, Colorado State University, 1618 Campus Delivery, Fort Collins, CO 80523, USA.
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Bell
authors.affiliation: Graduate School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Uesaka
authors.affiliation: 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.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Aizawa
authors.affiliation: Department of Environmental and Radiological Health Sciences, Colorado State University, 1618 Campus Delivery, Fort Collins, CO 80523, USA. Electronic address: Takamitsu.Kato@Colostate.edu.
authors.forename: Takamitsu A
authors.initials: TA
authors.lastname: Kato
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016466:CHO Cells; D049109:Cell Proliferation / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D020732:Cytogenetic Analysis / Q000379:methods; D004249:DNA Damage; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D012431:Rutin / Q000737:chemistry / Q000494:pharmacology; D012854:Sister Chromatid Exchange / Q000187:drug effects
chemical_list: D000975:Antioxidants; C016527:isoquercitrin; D012431:Rutin; D011794:Quercetin; D011065:Poly(ADP-ribose) Polymerases
keywords: Flavonoid; Glycoside; Micronuclei; Sister chromatid exchange