Obesity and Metabolism Laboratory, Biomedical Research Institute of Murcia (IMIB), 30120 Murcia, Spain.
Department of Biochemistry, Molecular Biology B and Immunology, School of Medicine, University of Murcia, Regional Campus of International Excellence "Campus Mare Nostrum", 30100 Murcia, Spain.
Int J Mol Sci. 2022 Nov 2;23(21):13400. doi: 10.3390/ijms232113400.
Acute myeloid leukemia (AML) is a cancer of the myeloid blood cells mainly treated with chemotherapy for cancer remission, but this non-selective treatment also induces numerous side effects. Investigations with bioactive compounds from plant-derived foods against cancer have increased in the last years because there is an urgent need to search for new anti-leukemic agents possessing higher efficacy and selectivity for AML cells and fewer negative side effects. In this study, we analyzed the anti-leukemic activity of several phytochemicals that are representative of the major classes of compounds present in cruciferous foods (glucosinolates, isothiocyanates, hydroxycinnamic acids, flavonols, and anthocyanins) in the human acute myeloid leukemia cell line HL-60. Our results revealed that among the different Brassica-derived compounds assayed, sulforaphane (SFN) (an aliphatic isothiocyanate) showed the most potent anti-leukemic activity with an IC value of 6 µM in dose-response MTT assays after 48 h of treatment. On the other hand, chlorogenic acid (a hydroxycinnamic acid) and cyanidin-3-glucoside (an anthocyanin) also displayed anti-leukemic potential, with IC values of 7 µM and 17 µM after 48 h of incubation, respectively. Importantly, these compounds did not show significant cell toxicity in macrophages-like differentiated cells at 10 and 25 µM, indicating that their cytotoxic effects were specific to AML cancer cells. Finally, we found that these three compounds were able to induce the NRF2/KEAP1 signaling pathway in a dose-dependent manner, highlighting SFN as the most potent NRF2 activator. Overall, the present evidence shed light on the potential for using foods and ingredients rich in anticancer bioactive phytochemicals from spp.
急性髓细胞白血病（AML）是一种主要通过化疗治疗的髓系血液系统癌症，以实现癌症缓解，但这种非选择性治疗也会引起许多副作用。近年来，人们对植物源性食物中的生物活性化合物治疗癌症的研究有所增加，因为迫切需要寻找新的抗白血病药物，这些药物对 AML 细胞具有更高的疗效和选择性，且副作用更少。在这项研究中，我们分析了几种植物化学物质对人急性髓细胞白血病细胞系 HL-60 的抗白血病活性，这些植物化学物质代表了十字花科蔬菜中存在的主要化合物类别（硫代葡萄糖苷、异硫氰酸酯、羟基肉桂酸、黄酮醇和花青素）。我们的研究结果表明，在所测试的不同源自 Brassica 的化合物中，萝卜硫素（SFN）（一种脂肪族异硫氰酸酯）在 48 小时的处理后，在剂量反应 MTT 测定中表现出最有效的抗白血病活性，IC 值为 6 µM。另一方面，绿原酸（一种羟基肉桂酸）和矢车菊素-3-葡萄糖苷（一种花青素）也表现出抗白血病潜力，分别在孵育 48 小时后的 IC 值为 7 µM 和 17 µM。重要的是，这些化合物在 10 和 25 µM 时在巨噬细胞样分化细胞中没有显示出显著的细胞毒性，这表明它们的细胞毒性作用是 AML 癌细胞特有的。最后，我们发现这三种化合物能够以剂量依赖的方式诱导 NRF2/KEAP1 信号通路，突出了 SFN 作为最有效的 NRF2 激活剂。总之，目前的证据表明，从 中使用富含抗癌生物活性植物化学物质的食物和成分具有潜力。
