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 S. Tyler, Stephen J. Freedland, Salvatore Pizzo

Research output: Contribution to journalArticle

17 Scopus citations

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)
Pages (from-to)E141-E148
JournalJournal of Surgical Research
Volume179
Issue number1
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

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

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