Combined Lycopene and Vitamin E Treatment Suppresses the Growth of PC-346C Human Prostate Cancer Cells in Nude Mice

Epidemiologic studies have repeatedly associated a high intake of lycopene and vitamin E with reduced prostate cancer risk. The present study examined the ability of the 2 compounds to reduce tumor growth and prostate-specific antigen (PSA) plasma levels in the PC-346C orthotopic mouse model of huma...

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Published in:	The Journal of nutrition 2006-05, Vol.136 (5), p.1287-1293
Main Authors:	Limpens, Jacqueline, Schröder, Fritz H, de Ridder, Corrina MA, Bolder, Cindy A, Wildhagen, Mark F, Obermüller-Jevic, Ute C, Krämer, Klaus, van Weerden, Wytske M
Format:	Article
Language:	eng
Subjects:	alpha-tocopherol animal models Animals Anticarcinogenic Agents - pharmacology Biological and medical sciences biomarkers Carotenoids - administration & dosage Carotenoids - pharmacology Cell Division - drug effects Cell Line, Tumor cell lines Cell Survival - drug effects chemoprevention delta-tocopherol diet therapy Dietary Supplements Feeding. Feeding behavior Fundamental and applied biological sciences. Psychology gamma-tocopherol Humans isomers liver Lycopene Male Mice Mice, Nude mortality neoplasm antigens nutrient availability Prostate cancer prostatic neoplasms Prostatic Neoplasms - pathology Risk factors Rodents Transplantation, Heterologous tumor xenograft model Tumors Vertebrates: anatomy and physiology, studies on body, several organs or systems Vitamin E Vitamin E - administration & dosage Vitamin E - pharmacology
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Summary:	Epidemiologic studies have repeatedly associated a high intake of lycopene and vitamin E with reduced prostate cancer risk. The present study examined the ability of the 2 compounds to reduce tumor growth and prostate-specific antigen (PSA) plasma levels in the PC-346C orthotopic mouse model of human prostate cancer. Three days after intraprostatic tumor injection, NMRI nu/nu mice were administered a daily oral dose of synthetic lycopene [5 or 50 mg/kg body weight (BW)], vitamin E in the form of α-tocopheryl acetate (5 or 50 mg/kg BW), a mixture of lycopene and vitamin E (5 mg/kg BW each), or vehicle. Intraprostatic tumor volume and plasma PSA concentrations were measured at regular intervals. Mice were killed when the tumor load exceeded 1000 mm3 or on d 95 when the study was terminated. Prostate and liver were analyzed by HPLC for lycopene isomers and α- and γ, δ-tocopherol concentrations. None of the single treatments significantly reduced tumor volume. In contrast, combined treatment with lycopene and vitamin E, at 5 mg/kg BW each, suppressed orthotopic growth of PC-346C prostate tumors by 73% at d 42 (P < 0.05) and increased median survival time by 40% from 47 to 66 d (P = 0.02). The PSA index (PSA:tumor volume ratio) did not differ between experimental groups, indicating that PSA levels were not selectively affected. Lycopene was detected only in mice supplemented with lycopene. As in humans, most tissue lycopene was in the cis-isomer conformation, whereas 77% trans-lycopene was used in the dosing material. Liver α-tocopherol concentrations were increased in mice supplemented with both 50 mg/kg (226%, P < 0.05) and 5 mg/kg vitamin E (41%, P < 0.05), whereas prostate α-tocopherol concentrations were increased only by the higher dose (83%, P < 0.05). Our data provide evidence that lycopene combined with vitamin E may inhibit the growth of prostate cancer and that PSA can serve as a biomarker of tumor response for this treatment regimen.
ISSN:	0022-3166 1541-6100