Resveratrol metabolites do not elicit early pro-apoptotic mechanisms in neuroblastoma cells

Jason D. Kenealey, Lalita Subramanian, Paul R. Van Ginkel, Soesiawati Darjatmoko, Mary J. Lindstrom, Veronika Somoza, Sunil K. Ghosh, Zhenlei Song, Richard P. Hsung, Glen S. Kwon, Kevin W. Eliceiri, Daniel M. Albert, Arthur S. Polans

Research output: Contribution to journalArticle

29 Scopus citations

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 [Ca2+]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.

Original languageEnglish (US)
Pages (from-to)4979-4986
Number of pages8
JournalJournal of Agricultural and Food Chemistry
Volume59
Issue number9
DOIs
StatePublished - May 11 2011

Keywords

  • Bioavailability
  • Calcium signaling
  • Neuroblastoma
  • Resveratrol

ASJC Scopus subject areas

  • Chemistry(all)
  • Agricultural and Biological Sciences(all)

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    Kenealey, J. D., Subramanian, L., Van Ginkel, P. R., Darjatmoko, S., Lindstrom, M. J., Somoza, V., Ghosh, S. K., Song, Z., Hsung, R. P., Kwon, G. S., Eliceiri, K. W., Albert, D. M., & Polans, A. S. (2011). Resveratrol metabolites do not elicit early pro-apoptotic mechanisms in neuroblastoma cells. Journal of Agricultural and Food Chemistry, 59(9), 4979-4986. https://doi.org/10.1021/jf104901g