Department of Nutrition, University of California, Davis, One Shields Ave, Davis, CA 95616, USA.
Exp Biol Med (Maywood). 2010 Jan;235(1):77-89. doi: 10.1258/ebm.2009.009184.
There is cumulative strong evidence that diets rich in flavanols can provide certain positive health benefits, particularly with respect to the cardiovascular system. Consequently, it has been suggested that increasing one's dietary intake of flavanols may be of benefit. Complicating this idea, there are reports that high intakes of certain flavonoids during pregnancy are associated with an increased risk for acute infant leukemia due to a poison effect of select polyphenolic compounds on DNA topoisomerase (topo) II activity that promotes aberrant chromosomal translocations. In the current study, we characterized the effects of select flavanols (epicatechin and catechin monomers), and select flavanol dimers and longer oligomers, on topo II activity, and on cellular toxicity in vitro. In contrast to the chemotherapeutic drug etoposide (VP16) and the flavonol quercetin, which strongly inhibited topo II activity and increased the formation of cleavage complexes demonstrating a poison effect, the flavanols epicatechin and catechin had little effect on topo II enzyme activity. Accordingly, several fold greater concentrations of the flavanols were required to achieve cellular toxicity similar to that of quercetin and VP16 in cultures of myeloid and lymphoid cells. Low cellular toxicity and limited topo II inhibition were also observed with a procyanidin-rich cocoa extract. Of all the flavanols tested, the dimers (B2, B5 and a mix of both) exerted the greatest inhibition of topo II and inhibited cellular proliferation rates at concentrations similar to quercetin. However, in contrast to quercetin, the dimers did not function as topo II poisons. Collectively, our in vitro data show that cocoa-derived flavanols have limited effects on topo II activity and cellular proliferation in cancer cell lines. We predict that these compounds are likely to have limited leukemogenic potential at physiological concentrations.
有大量确凿证据表明，富含黄烷醇的饮食可以带来某些健康益处，尤其是对心血管系统。因此，有人建议增加黄烷醇的摄入量可能有益。但复杂的是，有报道称，怀孕期间某些类黄酮的高摄入量与急性婴儿白血病的风险增加有关，这是由于某些多酚化合物对 DNA 拓扑异构酶（topo）II 活性的毒性作用，促进了异常染色体易位。在本研究中，我们研究了几种黄烷醇（表儿茶素和儿茶素单体）以及黄烷醇二聚体和更长的低聚物对 topo II 活性和体外细胞毒性的影响。与化疗药物依托泊苷（VP16）和类黄酮槲皮素不同，它们强烈抑制 topo II 活性并增加切割复合物的形成，表明具有毒性作用，黄烷醇表儿茶素和儿茶素对 topo II 酶活性几乎没有影响。因此，需要几倍更高浓度的黄烷醇才能达到与槲皮素和 VP16 相似的细胞毒性，在骨髓细胞和淋巴样细胞培养物中。富原花青素的可可提取物也表现出低细胞毒性和有限的 topo II 抑制作用。在所测试的所有黄烷醇中，二聚体（B2、B5 和两者的混合物）对 topo II 的抑制作用最大，并以与槲皮素相似的浓度抑制细胞增殖率。然而，与槲皮素不同的是，二聚体不能作为 topo II 的毒物。总的来说，我们的体外数据表明，可可衍生的黄烷醇对癌细胞系中的 topo II 活性和细胞增殖的影响有限。我们预测，这些化合物在生理浓度下可能具有有限的白血病形成潜力。
