Effects of lycopene and tomato paste extracts on DNA and lipid oxidation in LNCaP human prostate cancer cells.
Animal and epidemiological studies point to a cancer preventive/therapeutic role for tomato products and its antioxidant, lycopene. It is hypothesized that lycopene will behave as an antioxidant at low concentrations and as a prooxidant at high concentrations in LNCaP human prostate cancer cell culture systems. We characterized the antioxidant, and prooxidant effects of a hexane extract of tomato paste (TP) and water solubilized lycopene at different concentrations using a prostate cancer cell line. Placebo (5% triglyceride, Roche Inc.) was used as a control. After 6, 24 hr and 48 hr incubation, LNCaP cells were harvested and used for each measurement. Cellular proliferation was determined using the MTT colorimetric assay. Lycopene and TP hexane extract inhibited cell growth in a dose-dependent (0.1-50 microM lycopene) manner and growth inhibition was 55% and 35% at 1 microM lycopene and TP hexane extract, respectively after 48 hr incubation. The levels of 8-hydroxydeoxyguanosine/deoxyguanosine (an oxidative DNA damage product) was significantly increased starting at 5 microM lycopene from both TP hexane extract and pure lycopene after 24 and 48 hr incubation with no protection at the lower concentrations. Malondialdehyde formation (a lipid peroxidation product measured by HPLC separation of the MDA-TBA adduct) was significantly reduced at low concentrations (0.1-1 microM) of lycopene in all treatments. Clinically relevant concentrations of lycopene and the tomato fraction containing lycopene significantly reduced LNCaP cancer cell survival which can only be partially explained by increased DNA damage at high lycopene concentrations (> 5 microM). Low concentrations of lycopene acted as a lipid antioxidant but did not protect DNA.
Hwang
Eun-Sun
ES
Center for Agricultural Biomaterial, Seoul National University, San 56-1, Shillim-dong, Kwanak-gu, Seoul 151-742, Korea.
Bowen
Phyllis E
PE
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000975:Antioxidants / Q000494:pharmacology; D002338:Carotenoids / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004273:DNA, Neoplasm / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D006586:Hexanes; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D000077276:Lycopene; D018551:Solanum lycopersicum / Q000737:chemistry*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D016877:Oxidants / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000503:physiopathology*; D013858:Thiobarbiturates / Q000032:analysis
D000975:Antioxidants; D004273:DNA, Neoplasm; D006586:Hexanes; D016877:Oxidants; D010936:Plant Extracts; D013858:Thiobarbiturates; D002338:Carotenoids; D008315:Malondialdehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; C029684:thiobarbituric acid; D000077276:Lycopene