Breast cancer is of the leading causes of cancer-related deaths and the most frequently diagnosed cancer among females worldwide. Despite advancements in breast cancer therapy, the disease eventually progresses in most patients because of de novo or secondary resistance. Thus, discovering novel drugs with high effectiveness and low toxicity for systemic therapy is essential. In this study, we investigated whether a new oleanolic derivative N-((1-(4-fluorophenyl)-1H-1,2,3-triazol-4-yl)methyl)-2-methylene-3-oxo-olean-12-en-28-amide (ZQL-4c) exhibits potential anticancer effects against breast cancer. We determined that ZQL-4c strongly inhibited cell proliferation and invasion and induced G2/M phase arrest and apoptosis in breast cancer cells. We then found that ZQL-4c induced the production of reactive oxygen species (ROS). We then found that ZQL-4c significantly inhibited Notch-AKT signaling pathways that are related to oxidative stress. Taken together, this study is the first to show that ZQL-4c can significantly suppress the growth and invasion of breast cancer by blocking Notch-Akt signaling pathways, which are mainly regulated by ROS-mediated oxidative stress. Thus, ZQL-4c might be considered a novel and potential anticancer drug for breast cancer treatment.

中文翻译：

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N-((1-(4-Fluorophenyl)-1H-1,2,3-triazol-4-yl)methyl)-2-methylene-3-oxo-olean-12-en-28-amide 诱导人细胞凋亡乳腺癌细胞通过刺激氧化应激和抑制 Notch-Akt 信号通路

乳腺癌是癌症相关死亡的主要原因，也是全世界女性中最常被诊断出的癌症。尽管乳腺癌治疗取得了进展，但由于新发或继发性耐药，大多数患者的疾病最终会进展。因此，发现高效、低毒的全身治疗新药至关重要。在这项研究中，我们研究了一种新的齐墩果酸衍生物 N-((1-(4-fluorophenyl)-1H-1,2,3-triazol-4-yl)methyl)-2-methylene-3-oxo-olean- 12-en-28-amide (ZQL-4c) 对乳腺癌具有潜在的抗癌作用。我们确定 ZQL-4c 强烈抑制细胞增殖和侵袭，并诱导乳腺癌细胞的 G2/M 期停滞和凋亡。然后我们发现 ZQL-4c 诱导了活性氧 (ROS) 的产生。然后我们发现 ZQL-4c 显着抑制与氧化应激相关的 Notch-AKT 信号通路。综上所述，本研究首次表明 ZQL-4c 可通过阻断主要受 ROS 介导的氧化应激调节的 Notch-Akt 信号通路显着抑制乳腺癌的生长和侵袭。因此，ZQL-4c 可能被认为是一种用于治疗乳腺癌的新型和潜在的抗癌药物。