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

• Published in: The Journal of surgical research 2013-01, Vol.179 (1), p.e141-e148
• Main Authors: Osmond, Gregory W., MD, MPH, Masko, Elizabeth M., PhD, Tyler, Douglas S., MD, Freedland, Stephen J., MD, Pizzo, Salvatore, MD, PhD
• Format: Article
• Language: English
• Subjects: 3,5,4'-trihydroxy-trans-stilbene; 3,5-dihydroxy-4'-acetoxy-trans-stilbene; 4'-acetoxy resveratrol; Animals; Antineoplastic Agents - therapeutic use; Cell Line, Tumor; Cell Proliferation; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; In Vitro Techniques; Male; Melanoma; Melanoma - drug therapy; Melanoma - pathology; Mice; Mice, Nude; Prostate carcinoma; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - pathology; Resveratrol; Skin Neoplasms - drug therapy; Skin Neoplasms - pathology; Stilbenes - therapeutic use; Surgery; Time Factors; Treatment Outcome; Xenograft Model Antitumor Assays
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2012.02.057

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 ( P s < 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 P s > 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.