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.
  
  
  CONCLUSIONS
  Although in vitro data were promising, RESV and 4-ACE have limited potential as single agents in the treatment of prostate carcinoma and melanoma.
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Osmond
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Masko
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Tyler
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Freedland
authors.forename: Salvatore
authors.initials: S
authors.lastname: Pizzo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077185:Resveratrol; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013267:Stilbenes / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D013267:Stilbenes; C079138:3,5-dihydroxy-4-ethylstilbene; D000077185:Resveratrol