The United Graduate School of Agriculture Sciences, Kagoshima University, Kagoshima 890-0065, Japan.
Graduate School of Agriculture, Forestry and Fisheries, Kagoshima University, Kagoshima 890-0065, Japan.
Molecules. 2024 May 20;29(10):2408. doi: 10.3390/molecules29102408.
Quercetin, a flavonoid polyphenol found in many plants, has garnered significant attention due to its potential cancer chemoprevention. Our previous studies have shown that acetyl modification of the hydroxyl group of quercetin altered its antitumor effects in HepG2 cells. However, the antitumor effect in other cancer cells with different gene mutants remains unknown. In this study, we investigated the antitumor effect of quercetin and its methylated derivative 3,3',4',7--tetramethylquercetin (4Me-Q) and acetylated derivative 3,3',4',7--tetraacetylquercetin (4Ac-Q) on two human breast cancer cells, MCF-7 (wt-p53, caspase-3-ve) and MDA-MB-231 (mt-p53, caspase-3+ve). The results demonstrated that 4Ac-Q exhibited significant cell proliferation inhibition and apoptosis induction in both MCF-7 and MDA-MB-231 cells. Conversely, methylation of quercetin was found to lose the activity. The human apoptosis antibody array revealed that 4Ac-Q might induce apoptosis in MCF-7 cells via a p53-dependent pathway, while in MDA-MB-231 cells, it was induced via a caspase-3-dependent pathway. Furthermore, an evaluation using a superoxide inhibitor, MnTBAP, revealed 4Ac-Q-induced apoptosis in MCF-7 cells in a superoxide-independent manner. These findings provide valuable insights into the potential of acetylated quercetin as a new approach in cancer chemoprevention and offer new avenues for health product development.
槲皮素是一种存在于多种植物中的类黄酮多酚，因其具有潜在的癌症化学预防作用而受到广泛关注。我们之前的研究表明，槲皮素羟基的乙酰化修饰改变了其在 HepG2 细胞中的抗肿瘤作用。然而，在具有不同基因突变的其他癌细胞中，其抗肿瘤作用尚不清楚。在这项研究中，我们研究了槲皮素及其甲基化衍生物 3,3',4',7--四甲基槲皮素（4Me-Q）和乙酰化衍生物 3,3',4',7--四乙酰基槲皮素（4Ac-Q）对两种人乳腺癌细胞 MCF-7（wt-p53，caspase-3-ve）和 MDA-MB-231（mt-p53，caspase-3+ve）的抗肿瘤作用。结果表明，4Ac-Q 对 MCF-7 和 MDA-MB-231 细胞均表现出显著的细胞增殖抑制和凋亡诱导作用。相反，槲皮素的甲基化则失去了这种活性。人凋亡抗体阵列显示，4Ac-Q 可能通过 p53 依赖途径诱导 MCF-7 细胞凋亡，而在 MDA-MB-231 细胞中，它通过 caspase-3 依赖途径诱导凋亡。此外，使用超氧化物抑制剂 MnTBAP 进行的评估表明，4Ac-Q 以超氧化物非依赖的方式诱导 MCF-7 细胞凋亡。这些发现为乙酰化槲皮素作为癌症化学预防的新方法提供了有价值的见解，并为健康产品的开发提供了新的途径。
