Abstract

Flavonoids are phenolic substances with chemo-preventive and chemotherapeutic properties. They are widely found in fruits and vegetables. The polyphenols quercetin and curcumin have antioxidant, anti-inflammatory, anti-carcinogenic, and pro-apoptotic properties. They were successfully used against different human cancers, especially chronic myeloid leukemia cancer cells. We have previously investigated anti-proliferative and apoptotic effects of quercetin and curcumin combination in K562 cells. Our data showed that they had beneficial synergistic effects. Based on these findings, we aimed to clarify signaling pathways involved in synergistic combination treatment with quercetin and curcumin in these cells. Proteins were investigated by Western blotting and by confocal microscopy. Changes in several genes in 10 different pathways related to cell proliferation, apoptosis, cell cycle, inflammation, hypoxia and oxidative stress were observed. Combination of quercetin and curcumin was effective on genes that were particularly related to p53, NF-κB and TGF-α pathways. Down-regulatory (CDKN1B, AKT1, IFN-γ) and up-regulatory (BTG2, CDKN1A, FAS) effects on genes and related protein expressions may provide a multi-targeted therapy potential for chronic myeloid leukemia cancer cells without affecting healthy cells.

摘要

类黄酮是具有化学预防和化学治疗特性的酚类物质。它们广泛存在于水果和蔬菜中。多酚槲皮素和姜黄素具有抗氧化、抗炎、抗癌和促凋亡的特性。它们成功地用于对抗不同的人类癌症，尤其是慢性粒细胞白血病癌细胞。我们之前曾研究过槲皮素和姜黄素组合在 K562 细胞中的抗增殖和凋亡作用。我们的数据表明它们具有有益的协同效应。基于这些发现，我们旨在阐明这些细胞中槲皮素和姜黄素协同联合治疗所涉及的信号通路。通过蛋白质印迹和共聚焦显微镜研究蛋白质。观察到与细胞增殖、凋亡、细胞周期、炎症、缺氧和氧化应激相关的 10 种不同途径中几个基因的变化。槲皮素和姜黄素的组合对与 p53、NF-κB 和 TGF-α 通路特别相关的基因有效。下调（CDKN1B、AKT1、IFN-γ）和上调（BTG2、CDKN1A、FAS）对基因和相关蛋白表达的影响可能为慢性粒细胞白血病癌细胞提供多靶向治疗潜力，而不会影响健康细胞。