Physiologically attainable concentrations of lycopene induce mitochondrial apoptosis in LNCaP human prostate cancer cells.
Prostate cancer is the second leading cause of cancer deaths among men in the United States. Studies show that people with diets rich in tomato-based foods have reduced risks of cancer, viz., prostate cancer. This is attributed, in part, to lycopene, the most abundant carotenoid in tomatoes. Thus, we studied the effect of lycopene at physiologically attainable concentrations on apoptosis, cellular proliferation, and necrosis in LNCaP human prostate cancer cells. Cells at 37 degrees C and >80% confluency were treated with media alone (0.32% tetrahydrofuran vehicle) or with increasing concentrations (0.3-3.0 microM) of lycopene overnight. After washing monolayers, analyses by high-performance liquid chromatography (HPLC) showed that cellular accumulation of lycopene was 5.5 +/- 0.8, 14.0 +/- 3.2, and 36.7 +/- 12.3 pmole/10(6) cells for 0.3, 1.0, and 3.0 muM, respectively, and not detected in control cells. Lycopene did not alter cellular proliferation because bromodeoxyuridine (BrdU) incorporation and cell numbers were identical among groups. However, results of a 3[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay showed that mitochondrial function decreased 61%-83% with increasing concentrations of lycopene (P < 0.001). Cytotoxicity and necrosis did not contribute to this effect because lactate dehydrogenase (LDH) release (1.5%-1.8%) and trypan blue exclusion (89%-93%) were similar. Subsequently, we demonstrated that increasing concentrations of lycopene significantly (P < 0.05) reduced mitochondrial transmembrane potential, induced the release of mitochondrial cytochrome c, and increased annexin V binding, confirming induction of apoptosis. Thus, lycopene at physiologically relevant concentrations did not affect cellular proliferation or promote necrosis but clearly altered mitochondrial function and induced apoptosis in LNCaP human prostate cancer cells.
Hantz
Holly L
HL
Nutrition and Cancer Laboratory, The Pennsylvania State University, S-126 Henderson Building South, University Park, PA 16802, USA.
Young
Leeanne F
LF
Martin
Keith R
KR
D016588:Anticarcinogenic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002338:Carotenoids / Q000378:metabolism / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D003574:Cytochrome c Group / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D000077276:Lycopene; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D011471:Prostatic Neoplasms / Q000473:pathology; D014407:Tumor Cells, Cultured
D016588:Anticarcinogenic Agents; D003574:Cytochrome c Group; D002338:Carotenoids; D007770:L-Lactate Dehydrogenase; D001973:Bromodeoxyuridine; D000077276:Lycopene