In vitro and in vivo evaluation of resveratrol and 3,5-dihydroxy-4'- acetoxy-trans-stilbene in the treatment of human prostate carcinoma and melanoma

Gregory W. Osmond, Elizabeth M. Masko, Douglas Tyler, Stephen J. Freedland, Salvatore Pizzo

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Background: Resveratrol (RESV) is a naturally occurring compound that may possess anticancer capabilities in both prostate carcinoma and melanoma. Methods: The in vitro and in vivo cytotoxic activity of RESV and 3,5-dihydroxy-4'-acetoxy-trans-stilbene (4-ACE) was tested using cellular assays and a xenograft model. Five prostate carcinoma cell lines were used for in vitro evaluation. A melanoma cell line (Duke melanoma 738 [DM738]) and the prostate carcinoma line CWR22 were used for in vivo experiments. Mice were randomized to osmotic mini pumps with 200 μL of RESV (250 mg/mL), 4-ACE (335 mg/mL), or vehicle (50% dimethyl sulfoxide, 50% polyethylene glycol). Serum drug and metabolite levels were calculated by high-performance liquid chromatography with diode-array detection. Western blots were performed on treated tumors. Results were analyzed using a student's t-test, analysis of variance, and the Mann-Whitney rank sum test. Results: RESV and 4-ACE were cytotoxic in a time- and dose-dependent manner in all prostate carcinoma cell lines tested. Enhanced growth compared with controls was seen at the 24 h time point in four lines treated with RESV and two lines treated with 4-ACE (Ps < 0.048). In vivo, no difference in either tumor growth or postmortem tumor weight was detected in either DM738 (P = 0.555, P = 0.562) or CWR22 (P = 0.166, P = 0.811) xenografts treated with either drug. Serum drug levels did not correlate with tumor growth rates for any treatment group (all Ps > 0.11). Treated tumors demonstrated protein changes by western blot. Conclusion: Although in vitro data were promising, RESV and 4-ACE have limited potential as single agents in the treatment of prostate carcinoma and melanoma.

Original languageEnglish (US)
JournalJournal of Surgical Research
Volume179
Issue number1
DOIs
StatePublished - Jan 2013
Externally publishedYes

Fingerprint

Stilbenes
Prostate
Melanoma
Carcinoma
Cell Line
Therapeutics
Western Blotting
Nonparametric Statistics
Dimethyl Sulfoxide
Heterografts
resveratrol
In Vitro Techniques
Neoplasms
Analysis of Variance
High Pressure Liquid Chromatography
Students
Growth
Serum
Pharmaceutical Preparations
Proteins

Keywords

  • 3,5,4'-trihydroxy- trans-stilbene
  • 3,5-dihydroxy-4'-acetoxy-trans-stilbene
  • 4'-acetoxy resveratrol
  • Melanoma
  • Prostate carcinoma
  • Resveratrol

ASJC Scopus subject areas

  • Surgery
  • Medicine(all)

Cite this

In vitro and in vivo evaluation of resveratrol and 3,5-dihydroxy-4'- acetoxy-trans-stilbene in the treatment of human prostate carcinoma and melanoma. / Osmond, Gregory W.; Masko, Elizabeth M.; Tyler, Douglas; Freedland, Stephen J.; Pizzo, Salvatore.

In: Journal of Surgical Research, Vol. 179, No. 1, 01.2013.

Research output: Contribution to journalArticle

@article{6738213f02ed4e0fbccf3961d0fe67d0,
title = "In vitro and in vivo evaluation of resveratrol and 3,5-dihydroxy-4'- acetoxy-trans-stilbene in the treatment of human prostate carcinoma and melanoma",
abstract = "Background: Resveratrol (RESV) is a naturally occurring compound that may possess anticancer capabilities in both prostate carcinoma and melanoma. Methods: The in vitro and in vivo cytotoxic activity of RESV and 3,5-dihydroxy-4'-acetoxy-trans-stilbene (4-ACE) was tested using cellular assays and a xenograft model. Five prostate carcinoma cell lines were used for in vitro evaluation. A melanoma cell line (Duke melanoma 738 [DM738]) and the prostate carcinoma line CWR22 were used for in vivo experiments. Mice were randomized to osmotic mini pumps with 200 μL of RESV (250 mg/mL), 4-ACE (335 mg/mL), or vehicle (50{\%} dimethyl sulfoxide, 50{\%} polyethylene glycol). Serum drug and metabolite levels were calculated by high-performance liquid chromatography with diode-array detection. Western blots were performed on treated tumors. Results were analyzed using a student's t-test, analysis of variance, and the Mann-Whitney rank sum test. Results: RESV and 4-ACE were cytotoxic in a time- and dose-dependent manner in all prostate carcinoma cell lines tested. Enhanced growth compared with controls was seen at the 24 h time point in four lines treated with RESV and two lines treated with 4-ACE (Ps < 0.048). In vivo, no difference in either tumor growth or postmortem tumor weight was detected in either DM738 (P = 0.555, P = 0.562) or CWR22 (P = 0.166, P = 0.811) xenografts treated with either drug. Serum drug levels did not correlate with tumor growth rates for any treatment group (all Ps > 0.11). Treated tumors demonstrated protein changes by western blot. Conclusion: Although in vitro data were promising, RESV and 4-ACE have limited potential as single agents in the treatment of prostate carcinoma and melanoma.",
keywords = "3,5,4'-trihydroxy- trans-stilbene, 3,5-dihydroxy-4'-acetoxy-trans-stilbene, 4'-acetoxy resveratrol, Melanoma, Prostate carcinoma, Resveratrol",
author = "Osmond, {Gregory W.} and Masko, {Elizabeth M.} and Douglas Tyler and Freedland, {Stephen J.} and Salvatore Pizzo",
year = "2013",
month = "1",
doi = "10.1016/j.jss.2012.02.057",
language = "English (US)",
volume = "179",
journal = "Journal of Surgical Research",
issn = "0022-4804",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - In vitro and in vivo evaluation of resveratrol and 3,5-dihydroxy-4'- acetoxy-trans-stilbene in the treatment of human prostate carcinoma and melanoma

AU - Osmond, Gregory W.

AU - Masko, Elizabeth M.

AU - Tyler, Douglas

AU - Freedland, Stephen J.

AU - Pizzo, Salvatore

PY - 2013/1

Y1 - 2013/1

N2 - Background: Resveratrol (RESV) is a naturally occurring compound that may possess anticancer capabilities in both prostate carcinoma and melanoma. Methods: The in vitro and in vivo cytotoxic activity of RESV and 3,5-dihydroxy-4'-acetoxy-trans-stilbene (4-ACE) was tested using cellular assays and a xenograft model. Five prostate carcinoma cell lines were used for in vitro evaluation. A melanoma cell line (Duke melanoma 738 [DM738]) and the prostate carcinoma line CWR22 were used for in vivo experiments. Mice were randomized to osmotic mini pumps with 200 μL of RESV (250 mg/mL), 4-ACE (335 mg/mL), or vehicle (50% dimethyl sulfoxide, 50% polyethylene glycol). Serum drug and metabolite levels were calculated by high-performance liquid chromatography with diode-array detection. Western blots were performed on treated tumors. Results were analyzed using a student's t-test, analysis of variance, and the Mann-Whitney rank sum test. Results: RESV and 4-ACE were cytotoxic in a time- and dose-dependent manner in all prostate carcinoma cell lines tested. Enhanced growth compared with controls was seen at the 24 h time point in four lines treated with RESV and two lines treated with 4-ACE (Ps < 0.048). In vivo, no difference in either tumor growth or postmortem tumor weight was detected in either DM738 (P = 0.555, P = 0.562) or CWR22 (P = 0.166, P = 0.811) xenografts treated with either drug. Serum drug levels did not correlate with tumor growth rates for any treatment group (all Ps > 0.11). Treated tumors demonstrated protein changes by western blot. Conclusion: Although in vitro data were promising, RESV and 4-ACE have limited potential as single agents in the treatment of prostate carcinoma and melanoma.

AB - Background: Resveratrol (RESV) is a naturally occurring compound that may possess anticancer capabilities in both prostate carcinoma and melanoma. Methods: The in vitro and in vivo cytotoxic activity of RESV and 3,5-dihydroxy-4'-acetoxy-trans-stilbene (4-ACE) was tested using cellular assays and a xenograft model. Five prostate carcinoma cell lines were used for in vitro evaluation. A melanoma cell line (Duke melanoma 738 [DM738]) and the prostate carcinoma line CWR22 were used for in vivo experiments. Mice were randomized to osmotic mini pumps with 200 μL of RESV (250 mg/mL), 4-ACE (335 mg/mL), or vehicle (50% dimethyl sulfoxide, 50% polyethylene glycol). Serum drug and metabolite levels were calculated by high-performance liquid chromatography with diode-array detection. Western blots were performed on treated tumors. Results were analyzed using a student's t-test, analysis of variance, and the Mann-Whitney rank sum test. Results: RESV and 4-ACE were cytotoxic in a time- and dose-dependent manner in all prostate carcinoma cell lines tested. Enhanced growth compared with controls was seen at the 24 h time point in four lines treated with RESV and two lines treated with 4-ACE (Ps < 0.048). In vivo, no difference in either tumor growth or postmortem tumor weight was detected in either DM738 (P = 0.555, P = 0.562) or CWR22 (P = 0.166, P = 0.811) xenografts treated with either drug. Serum drug levels did not correlate with tumor growth rates for any treatment group (all Ps > 0.11). Treated tumors demonstrated protein changes by western blot. Conclusion: Although in vitro data were promising, RESV and 4-ACE have limited potential as single agents in the treatment of prostate carcinoma and melanoma.

KW - 3,5,4'-trihydroxy- trans-stilbene

KW - 3,5-dihydroxy-4'-acetoxy-trans-stilbene

KW - 4'-acetoxy resveratrol

KW - Melanoma

KW - Prostate carcinoma

KW - Resveratrol

UR - http://www.scopus.com/inward/record.url?scp=84870705922&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84870705922&partnerID=8YFLogxK

U2 - 10.1016/j.jss.2012.02.057

DO - 10.1016/j.jss.2012.02.057

M3 - Article

VL - 179

JO - Journal of Surgical Research

JF - Journal of Surgical Research

SN - 0022-4804

IS - 1

ER -