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

doi:10.1021/jf104901g

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 journal › Article › peer-review

37 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 language	English (US)
Pages (from-to)	4979-4986
Number of pages	8
Journal	Journal of Agricultural and Food Chemistry
Volume	59
Issue number	9
DOIs	https://doi.org/10.1021/jf104901g
State	Published - May 11 2011
Externally published	Yes

Keywords

Bioavailability
Calcium signaling
Neuroblastoma
Resveratrol

ASJC Scopus subject areas

General Chemistry
General Agricultural and Biological Sciences

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10.1021/jf104901g

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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

Kenealey, JD, Subramanian, L, Van Ginkel, PR, Darjatmoko, S, Lindstrom, MJ, Somoza, V, Ghosh, SK, Song, Z, Hsung, RP, Kwon, GS, Eliceiri, KW, Albert, DM & Polans, AS 2011, 'Resveratrol metabolites do not elicit early pro-apoptotic mechanisms in neuroblastoma cells', Journal of Agricultural and Food Chemistry, vol. 59, no. 9, pp. 4979-4986. https://doi.org/10.1021/jf104901g

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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 [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.",

keywords = "Bioavailability, Calcium signaling, Neuroblastoma, Resveratrol",

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

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doi = "10.1021/jf104901g",

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AU - Lindstrom, Mary J.

AU - Somoza, Veronika

AU - Ghosh, Sunil K.

AU - Song, Zhenlei

AU - Hsung, Richard P.

AU - Kwon, Glen S.

AU - Eliceiri, Kevin W.

AU - Albert, Daniel M.

AU - Polans, Arthur S.

PY - 2011/5/11

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N2 - 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.

AB - 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.

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

Abstract

Keywords

ASJC Scopus subject areas

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