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

Abstract

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 alpha-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 mm(3) or on d 95 when the study was terminated. Prostate and liver were analyzed by HPLC for lycopene isomers and alpha- and gamma, delta-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 alpha-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 alpha-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.

Anti-Oxidant Status of Male Adults with and without Prostate Cancer in Ibadan, Nigeria

“…Lycopene is a promising component for the chemoprevention of prostate cancer [30] Regular intake of lycopene has been repeatedly associated with a reduced risk of developing the disease [31]. The significant inverse association detected between lycopene intake and prostate cancer in this study is consistent with the findings that evidence exists for inverse associations of dietary intake of lycopene with PC [13] [32] [33].…”

Multitargeted therapy of cancer by lycopene

“…At dosages of 100 and 300 mg/kg lycopene, the tumor growth rates were inhibited 55.6 and 75.8%, respectively. In contrast, Limpens et al [52] used the PC-346C orthotopic mouse model of prostate cancer but found no effect on tumor volume when lycopene was administered orally at 5 or 50 mg/kg. However, tumor volume was reduced with lycopene was combined with α-tocopherol acetate.…”

Anacardic acid (6-pentadecylsalicylic acid) induces apoptosis of prostate cancer cells through inhibition of androgen receptor and activation of p53 signaling

“…Androgen is an important biological effector of prostate cancer progression (17). Many studies have demonstrated that phytochemicals can effectively inhibit the apoptosis and proliferation of prostate cancer cells (18)(19)(20)(21)(22). Chun et al reported inhibition of cell viability and apoptosis of Pca cells treated by andrographolide, which is extracted from a medicinal plant (23).…”