title: Resveratrol metabolites do not elicit early pro-apoptotic mechanisms in neuroblastoma cells.
abstract: Resveratrol, a nontoxic polyphenol, has been shown to inhibit tumor growth in a xenograft mouse model of neuroblasoma. However, resveratrol is rapidly metabolized, mainly to its glucuronidated and sulfated derivatives. This study demonstrates that resveratrol alone, and not the glucuronidated or sulfated metabolites, is taken up into tumor cells, induces a rise in [Ca(2+)](i), and ultimately leads to a decrease in tumor cell viability. A new water-soluble resveratrol formulation was delivered directly at the site of the tumor in a neuroblastoma mouse model. The amount of unmodified resveratrol associated with the tumor increased more than 1000-fold. The increase of unmodified resveratrol associated with the tumor resulted in tumor regression. The number of residual tumor cells that remained viable also decreased as the ratio of the metabolites relative to unmodified resveratrol declined.
authors.affiliation: Department of Biomolecular Chemistry, Medical Science Center, University of Wisconsin, Madison, Wisconsin 53705, United States.
authors.forename: Jason D
authors.initials: JD
authors.lastname: Kenealey
authors.forename: Lalita
authors.initials: L
authors.lastname: Subramanian
authors.forename: Paul R
authors.initials: PR
authors.lastname: Van Ginkel
authors.forename: Soesiawati
authors.initials: S
authors.lastname: Darjatmoko
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Lindstrom
authors.forename: Veronika
authors.initials: V
authors.lastname: Somoza
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Ghosh
authors.forename: Zhenlei
authors.initials: Z
authors.lastname: Song
authors.forename: Richard P
authors.initials: RP
authors.lastname: Hsung
authors.forename: Glen S
authors.initials: GS
authors.lastname: Kwon
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Eliceiri
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Albert
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Polans
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009447:Neuroblastoma / Q000188:drug therapy / Q000503:physiopathology*; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage* / Q000378:metabolism*
chemical_list: D013267:Stilbenes; D000077185:Resveratrol