Department of Surgery, E-Da Cancer Hospital, Kaohsiung 82445, Taiwan.
School of Medicine, College of Medicine, I-Shou University, Kaohsiung 82445, Taiwan.
Molecules. 2021 Oct 26;26(21):6452. doi: 10.3390/molecules26216452.
Cancer stem cells (CSCs) are subpopulations of tumor masses with unique abilities in self-renewal, stemness maintenance, drug resistance, and the promotion of cancer recurrence. Recent studies have suggested that breast CSCs play essential roles in chemoresistance. Therefore, new agents that selectively target such cells are urgently required. Reactive oxygen species (ROS)-producing enzymes are the reason for an elevated tumor oxidant status. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor, which upon detecting cellular oxidative stress, binds to the promoter region of antioxidant genes. By triggering a cytoprotective response, Nrf2 maintains cellular redox status. Cripto-1 participates in the self-renewal of CSCs. Herein, luteolin, a flavonoid found in extract, was determined to inhibit the expressions of stemness-related transcriptional factors, the ATP-binding cassette transporter G2 (ABCG2), CD44, aldehyde dehydrogenase 1 activity as well as the sphere formation properties of breast CSCs. Furthermore, luteolin suppressed the protein expressions of Nrf2, heme oxygenase 1 (HO-1), and Cripto-1 which have been determined to contribute critically to CSC features. The combination of luteolin and the chemotherapeutic drug, Taxol, resulted in enhanced cytotoxicity to breast cancer cells. These findings suggest that luteolin treatment significantly attenuated the hallmarks of breast cancer stemness by downregulating Nrf2-mediated expressions. Luteolin constitutes a potential agent for use in cancer stemness-targeted breast cancer treatments.
癌症干细胞（CSCs）是肿瘤组织中具有独特自我更新、干细胞维持、耐药性和促进癌症复发能力的亚群。最近的研究表明，乳腺 CSCs 在化疗耐药中发挥着重要作用。因此，迫切需要新的、能选择性靶向这些细胞的药物。产生活性氧（ROS）的酶是肿瘤氧化剂状态升高的原因。核因子红细胞 2 相关因子 2（Nrf2）是一种转录因子，当检测到细胞氧化应激时，它会与抗氧化基因的启动子区域结合。通过触发细胞保护反应，Nrf2 维持细胞的氧化还原状态。Cripto-1 参与 CSCs 的自我更新。在此，研究人员发现，木犀草素是从 中提取的一种类黄酮，可以抑制干性相关转录因子、ATP 结合盒转运蛋白 G2（ABCG2）、CD44、醛脱氢酶 1 活性以及乳腺 CSCs 的球体形成特性。此外，木犀草素还抑制了 Nrf2、血红素加氧酶 1（HO-1）和 Cripto-1 的蛋白表达，这两种蛋白已被确定对 CSC 特征有重要贡献。木犀草素与化疗药物紫杉醇联合使用，可增强乳腺癌细胞的细胞毒性。这些发现表明，木犀草素通过下调 Nrf2 介导的表达，显著减弱了乳腺癌 CSCs 的特征。木犀草素构成了用于癌症干细胞靶向治疗乳腺癌的潜在药物。
