1-Dehydro-6-Gingerdione Exerts Anticancer Effects on MDA-MB-231 Cells and in the Xenograft Mouse Model by Promoting the Ferroptosis Pathway.

IF 6.1 2区 医学 Q1 CHEMISTRY, MEDICINAL
Thi Hoa My Tran, Sanjeevram Dhandapani, Samad Abdus, Yeon-Ju Kim
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引用次数: 0

Abstract

Breast cancer (BC) is the most prevalent malignancy among women, with millions of newly diagnosed cases emerging annually. Therefore, identifying novel pharmaceuticals for therapeutic purposes is imperative. Several natural compounds and their products have demonstrated potential in the treatment of cancer. This study examined the effects of the ginger derivative 1-dehydro-6-gingerdione (1-D-6-G) on BC and its mechanisms of action. MTT and colony formation assays were used to check the anticancer effect of 1-D-6-G. Then the anticancer mechanism of 1-D-6-G was predicted using proteomics analysis. The molecular pathway was verified by qRT-PCR and immunobloting analysis. Additionally, the anticancer properties of 1-D-6-G were investigated in vivo using xenograft mice model. Finally, an in silico study was conducted to examine the interaction of 1-D-6-G and pathway-related proteins. MTT and colony formation assay results indicated that 1-D-6-G has potent cytotoxic properties against BC cells. Proteomic analysis revealed that the anticancer mechanism of 1-D-6-G on MDA-MB-231 cells is associated with the ferroptosis signaling pathway. In addition, qRT-PCR and immunoblotting analyses revealed that the cytotoxic effects of 1-D-6-G on MDA-MB-231 cells were associated with ferroptosis signaling induction. Our in vivo results further confirmed the in vitro findings. The administration of 1-D-6-G for 14 days exhibited anticancer properties in xenograft mice by stimulating the ferroptosis pathway without causing damage to essential organs such as the liver and kidneys. Additionally, in silico results confirmed the structural stability of the molecular interaction between 1-D-6-G and ferroptosis target proteins. Our findings indicate that 1-D-6-G has the potential to serve as a novel therapeutic agent for inhibiting BC progression by targeting the ferroptosis pathway.

1-脱氢-6-姜酮通过促进铁氧化途径对 MDA-MB-231 细胞和异种移植小鼠模型发挥抗癌作用
乳腺癌(BC)是女性中发病率最高的恶性肿瘤,每年新确诊的病例数以百万计。因此,确定用于治疗的新型药物势在必行。一些天然化合物及其产品已被证明具有治疗癌症的潜力。本研究探讨了生姜衍生物 1-脱氢-6-姜酮(1-D-6-G)对 BC 的影响及其作用机制。研究采用 MTT 和菌落形成试验来检测 1-D-6-G 的抗癌效果。然后利用蛋白质组学分析预测了 1-D-6-G 的抗癌机制。通过 qRT-PCR 和免疫印迹分析验证了分子途径。此外,还利用异种移植小鼠模型对 1-D-6-G 的抗癌特性进行了体内研究。最后,研究人员还对 1-D-6-G 与通路相关蛋白的相互作用进行了硅学研究。MTT 和集落形成试验结果表明,1-D-6-G 对 BC 细胞具有强大的细胞毒性。蛋白质组分析表明,1-D-6-G 对 MDA-MB-231 细胞的抗癌机制与铁突变信号通路有关。此外,qRT-PCR 和免疫印迹分析表明,1-D-6-G 对 MDA-MB-231 细胞的细胞毒性作用与诱导铁变态反应信号通路有关。我们的体内研究结果进一步证实了体外研究结果。在异种移植小鼠体内连续 14 天服用 1-D-6-G 可通过刺激铁蛋白沉积途径发挥抗癌作用,而不会对肝脏和肾脏等重要器官造成损害。此外,硅学研究结果证实,1-D-6-G 与铁突变靶蛋白之间的分子相互作用具有结构稳定性。我们的研究结果表明,1-D-6-G 有潜力成为一种新型治疗药物,通过靶向铁蜕变途径抑制 BC 的进展。
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来源期刊
Phytotherapy Research
Phytotherapy Research 医学-药学
CiteScore
12.80
自引率
5.60%
发文量
325
审稿时长
2.6 months
期刊介绍: Phytotherapy Research is an internationally recognized pharmacological journal that serves as a trailblazing resource for biochemists, pharmacologists, and toxicologists. We strive to disseminate groundbreaking research on medicinal plants, pushing the boundaries of knowledge and understanding in this field. Our primary focus areas encompass pharmacology, toxicology, and the clinical applications of herbs and natural products in medicine. We actively encourage submissions on the effects of commonly consumed food ingredients and standardized plant extracts. We welcome a range of contributions including original research papers, review articles, and letters. By providing a platform for the latest developments and discoveries in phytotherapy, we aim to support the advancement of scientific knowledge and contribute to the improvement of modern medicine.
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