Food & Function, 2016, 7(8).

Bilberry extract, its major polyphenolic compounds, and the soy isoflavone genistein antagonize the cytostatic drug erlotinib in human epithelial cells

G. Aichinger, G. Pahlke, L. J. Nagel, et al

Department of Food Chemistry and Toxicology, University of Vienna, Waehringerstr. 38, A-1090 Vienna, Austria

Erlotinib (Tarceva®) is a chemotherapeutic drug approved for the treatment of pancreatic cancer and non-small cell lung cancer. Its primary mode of action is the inhibition of the epidermal growth factor receptor (EGFR), a receptor tyrosine kinase (RTK). Recently, RTK-inhibiting polyphenols have been reported to interact synergistically with erlotinib. Furthermore some anthocyanidins and anthocyanin-rich berry extracts have been reported to inhibit tyrosine kinases, including the EGFR, which raises the question of potential interactions with erlotinib. Polyphenol-rich preparations such as berry- or soy-based products are commercially available as food supplements. In the present study we tested a bilberry extract, its major anthocyanin and potential intestinal degradation products, as well as genistein, with respect to possible interactions with erlotinib. Cell growth inhibition was assessed using the sulforhodamine B assay, while interactions with EGFR phosphorylation were analyzed by SDS-PAGE/western blotting with subsequent immunodetection. Genistein, bilberry extract, delphinidin-3-O-glucoside and delphinidin were found to antagonize erlotinib whereas phloroglucinol aldehyde was found to enhance cytostatic effects of the drug on human epithelial A431 cells. Genistein also antagonized the EGFR inhibitory effects of erlotinib, whereas bilberry anthocyanins showed no significant interactions in this regard. Our data indicate that different polyphenols are potentially able to impair the cytostatic effect of erlotinib in vitro. Genistein interacts via the modulation of erlotinib-mediated EGFR inhibition whereas bilberry anthocyanins modulated the growth-inhibitory effect of erlotinib without affecting EGFR phosphorylation, thus indicating a different mechanism of interference.

英国《食品与功效》, 2016, 7(8).

越桔提取物，其主要的多酚化合物和大豆异黄酮染料木黄酮拮抗人上皮细胞中的细胞抑制药物厄洛替尼

食品化学和毒理学，维也纳大学，38，A-1090 维也纳奥地利

厄洛替尼 (Tarceva®) 是批准用于治疗胰腺癌和非小细胞肺癌化疗药物。其主要方式是对表皮生长因子受体 (EGFR)，受体酪氨酸激酶 (RTK) 有抑制作用。最近，有报道 RTK 抑制多酚与厄洛替尼协同作用。此外一些花色素和莓果富含花青素的提取物有报道是抑制酪氨酸激酶，包括表皮生长因子，这就引起了潜在的相互作用与厄洛替尼的问题。富含多酚的浆果或豆奶产品市面上作为食品补充剂。在本研究中我们测试越橘提取物、其主要花色苷和潜在肠道降解产物，以及金雀异黄素对可能的相互作用与厄洛替尼。虽然与 EGFR 磷酸化的交互进行 SDS-PAGE/蛋白质印迹与后续免疫使用磺基罗丹明B的检测，评估细胞生长的抑制作用。金雀异黄素，越橘提取物、飞燕草色素-3-葡萄糖苷和飞燕草色素被发现拮抗厄洛替尼，而间苯三酚醛被发现增强药物对人上皮 A431细胞的细胞生长抑制作用。染料木黄酮还拮抗 EGFR 抑制作用的厄洛替尼，而蓝莓花青素在这方面表现没有显著的交互作用。我们的数据表明，不同的茶多酚是潜在的能够损害厄洛替尼在体外增殖抑制作用。金雀异黄素进行交互，通过调制的厄洛替尼介导的 EGFR 抑制作用而蓝莓花青素调制厄洛替尼的生长抑制作用而不会影响 EGFR 磷酸化，从而指示一个不同的机制的干扰。