Hantz Holly L, Young Leeanne F, Martin Keith R
Nutrition and Cancer Laboratory, The Pennsylvania State University, S-126 Henderson Building South, University Park, PA 16802, USA.
Exp Biol Med (Maywood). 2005 Mar;230(3):171-9. doi: 10.1177/153537020523000303.
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.
前列腺癌是美国男性癌症死亡的第二大主要原因。研究表明，饮食中富含以番茄为基础的食物的人患癌症的风险降低，即前列腺癌。这部分归因于番茄红素，它是番茄中含量最丰富的类胡萝卜素。因此，我们研究了生理上可达到的浓度的番茄红素对LNCaP人前列腺癌细胞凋亡、细胞增殖和坏死的影响。将处于37摄氏度且汇合度>80%的细胞单独用培养基（0.32%四氢呋喃载体）或用浓度递增（0.3 - 3.0 microM）的番茄红素处理过夜。洗涤单层细胞后，通过高效液相色谱（HPLC）分析表明，对于0.3、1.0和3.0 microM的番茄红素，细胞内积累量分别为5.5±0.8、14.0±3.2和36.7±12.3 pmole/10(6)细胞，而在对照细胞中未检测到。番茄红素没有改变细胞增殖，因为各组之间溴脱氧尿苷（BrdU）掺入量和细胞数量相同。然而，3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴盐（MTT）试验结果表明，随着番茄红素浓度的增加，线粒体功能下降了61% - 83%（P < 0.001）。细胞毒性和坏死对此效应没有贡献，因为乳酸脱氢酶（LDH）释放（1.5% - 1.8%）和台盼蓝排斥率（89% - 93%）相似。随后，我们证明随着番茄红素浓度的增加，显著（P < 0.05）降低了线粒体跨膜电位，诱导了线粒体细胞色素c的释放，并增加了膜联蛋白V结合，证实了凋亡的诱导。因此，生理相关浓度的番茄红素不影响细胞增殖或促进坏死，但明显改变了LNCaP人前列腺癌细胞的线粒体功能并诱导了凋亡。
