Soleas G J, Goldberg D M, Grass L, Levesque M, Diamandis E P
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Clin Biochem. 2001 Jul;34(5):415-20. doi: 10.1016/s0009-9120(01)00246-6.
The p53 gene is an established tumor suppressor and an inducer of apoptosis. We here attempt to determine whether the putative anticarcinogenic properties attributed to red wine and its polyphenolic constituents depend, at least in part, upon their ability to modulate p53 expression in cancer cells.
Three human breast cancer cell lines (MCF-7, T47D; MDA-MB-486) and one human colon cancer cell line [Colo 320 HSR (+)] were treated for 24-h with each of four polyphenols [quercetin; (+)-catechin, trans-resveratrol; caffeic acid] at concentrations ranging from 10(-7) M to 10(-4) M, after which, p53 concentrations were measured in cell lysates by a time-resolved fluorescence immunoassay.
None of the polyphenols tested affected p53 expression in the breast cancer cell lines T-47D and MDA-MB-486. p53 content of MCF-7 breast cancer cells (wild-type) was increased by caffeic acid, decreased by resveratrol, and showed a twofold increase with catechin, that reached borderline statistical significance; however, none of these effects were dose-responsive. Colo 320 HSR (+) cells (with a mutant p53 gene) had lower p53 content upon stimulation, reaching borderline statistical significance, but without being dose-responsive, in the presence of caffeic acid and resveratrol. Apart from toxicity at 10(-4) M, quercetin had no effect upon these four cell lines.
The observed p53 concentration changes upon stimulation by polyphenols are relatively small, do not follow a uniform pattern in the four cell lines tested, and do not exhibit a dose-response effect. For these reasons, we speculate that the putative anticarcinogenic properties of wine polyphenols are unlikely to be mediated by modulation of p53 gene expression.
p53基因是一种公认的肿瘤抑制因子和细胞凋亡诱导剂。我们在此试图确定红酒及其多酚成分所具有的假定抗癌特性是否至少部分取决于它们调节癌细胞中p53表达的能力。
用四种多酚（槲皮素、（+）-儿茶素、反式白藜芦醇、咖啡酸），浓度范围为10^(-7) M至10^(-4) M，分别处理三种人乳腺癌细胞系（MCF-7、T47D、MDA-MB-486）和一种人结肠癌细胞系[Colo 320 HSR(+)]24小时，之后通过时间分辨荧光免疫测定法测量细胞裂解物中的p53浓度。
所测试的多酚均未影响乳腺癌细胞系T-47D和MDA-MB-486中的p53表达。咖啡酸使MCF-7乳腺癌细胞（野生型）的p53含量增加，白藜芦醇使其降低，儿茶素使其增加两倍，达到边缘统计学显著性；然而，这些作用均无剂量依赖性。Colo 320 HSR(+)细胞（具有突变的p53基因）在受到刺激后p53含量降低，达到边缘统计学显著性，但在咖啡酸和白藜芦醇存在的情况下无剂量依赖性。除了在10^(-4) M时有毒性外，槲皮素对这四种细胞系无影响。
多酚刺激后观察到的p53浓度变化相对较小，在测试的四种细胞系中未呈现统一模式，也未表现出剂量反应效应。基于这些原因，我们推测红酒多酚的假定抗癌特性不太可能通过调节p53基因表达来介导。
