Department of Basic Sciences, Preparatory Year Deanship, King Faisal University, Al Ahsa 31982, Saudi Arabia.
Department of Public Health, College of Applied Medical Sciences, King Faisal University, Al Ahsa 31982, Saudi Arabia.
Molecules. 2023 Mar 24;28(7):2925. doi: 10.3390/molecules28072925.
Cancer incidence varies around the globe, implying a relationship between food and cancer risk. Plant polyphenols are a class of secondary metabolites that have recently attracted attention as possible anticancer agents. The subclass of polyphenols, known as isoflavones, includes genistein and daidzein, which are present in soybeans and are regarded as potent chemopreventive agents. According to epidemiological studies, those who eat soy have a lower risk of developing certain cancers. Several mechanisms for the anticancer effects of isoflavones have been proposed, but none are conclusive. We show that isoflavones suppress prostate cancer cell growth by mobilizing endogenous copper. The copper-specific chelator neocuproine decreases the apoptotic potential of isoflavones, whereas the iron and zinc chelators desferroxamine mesylate and histidine do not, confirming the role of copper. Reactive oxygen species (ROS) scavengers reduce isoflavone-induced apoptosis in these cells, implying that ROS are cell death effectors. Our research also clearly shows that isoflavones interfere with the expression of the two copper transporter genes, and , in cancerous cells. Copper levels are widely known to be significantly raised in all malignancies, and we confirm that isoflavones can target endogenous copper, causing prooxidant signaling and, eventually, cell death. These results highlight the importance of copper dynamics within cancer cells and provide new insight into the potential of isoflavones as cancer-fighting nutraceuticals.
癌症的发病率在全球范围内存在差异，这表明食物与癌症风险之间存在一定关系。植物多酚是一类次生代谢产物，最近作为潜在的抗癌药物引起了人们的关注。多酚的亚类，即异黄酮，包括大豆中存在的染料木黄酮和大豆苷元，被认为是有效的化学预防剂。根据流行病学研究，食用大豆的人患某些癌症的风险较低。已经提出了异黄酮抗癌作用的几种机制，但没有一种是结论性的。我们表明，异黄酮通过动员内源性铜来抑制前列腺癌细胞生长。铜特异性螯合剂去铁胺降低了异黄酮的凋亡潜力，而铁和锌螯合剂甲磺酸去铁胺和组氨酸则没有，这证实了铜的作用。活性氧（ROS）清除剂降低了这些细胞中异黄酮诱导的细胞凋亡，这表明 ROS 是细胞死亡效应物。我们的研究还清楚地表明，异黄酮会干扰癌细胞中两种铜转运基因 和 的表达。众所周知，所有恶性肿瘤中的铜水平都会显著升高，我们证实异黄酮可以靶向内源性铜，导致促氧化剂信号传递，并最终导致细胞死亡。这些结果强调了癌症细胞内铜动态的重要性，并为异黄酮作为抗癌营养保健品的潜力提供了新的见解。
