Hsieh Wen-Chi, Lin Chun-Yu, Wu Hsuan-Cheng, Lo Huang-Wei, Ko Chiung-Yuan, Chuang Jian-Ying, Hsu Tsung-I, Tseng Tsui-Hwa, Huang Teng-Wei, Wang Shao-Ming
Neuroscience and Brain Disease Center, China Medical University, Taichung, Taiwan.
Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, Taiwan.
Discov Oncol. 2025 Aug 4;16(1):1463. doi: 10.1007/s12672-025-03279-4.
Calanthe arisanensis, a traditional medicinal orchid, contains Calanquinone A, a quinone-type compound with reported anticancer properties. Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with limited treatment options and a poor prognosis. This study investigates the molecular mechanisms underlying the antiproliferative and antimigratory effects of Calanquinone A in GBM. Human GBM cell lines (U87MG) and patient-derived primary GBM cells (Pt#3) were treated with Calanquinone A (1-2.5 µM), and effects on cell viability, proliferation, and migration were assessed using CCK-8, trypan blue exclusion, colony formation, wound healing, transwell migration, and F-actin staining assays. Calanquinone A significantly reduced GBM cell viability and migration. Western blot analysis revealed that Calanquinone A inhibited STAT3 phosphorylation at Tyr705, leading to downregulation of its downstream targets c-Myc and MMP9. STAT3 overexpression reversed these effects, confirming the involvement of STAT3-dependent pathways. In a mouse xenograft model, Calanquinone A suppressed tumor formation in vivo. Molecular docking analysis further revealed a potential direct interaction between Calanquinone A and STAT3, supporting a direct mechanism of action. These findings demonstrate that Calanquinone A exerts potent antitumor effects in glioblastoma by targeting the STAT3/c-Myc and STAT3/MMP9 signaling axes, supporting its potential as a natural STAT3-targeting agent for GBM therapy.
阿里山虾脊兰是一种传统药用兰花，含有卡拉醌A，一种据报道具有抗癌特性的醌类化合物。多形性胶质母细胞瘤（GBM）是一种侵袭性很强的脑肿瘤，治疗选择有限且预后较差。本研究调查了卡拉醌A对GBM细胞的抗增殖和抗迁移作用的分子机制。用卡拉醌A（1 - 2.5 μM）处理人GBM细胞系（U87MG）和患者来源的原发性GBM细胞（Pt#3），并使用CCK - 8、台盼蓝排斥、集落形成、伤口愈合、Transwell迁移和F - 肌动蛋白染色试验评估其对细胞活力、增殖和迁移的影响。卡拉醌A显著降低了GBM细胞的活力和迁移能力。蛋白质印迹分析显示，卡拉醌A抑制了STAT3在Tyr705位点的磷酸化，导致其下游靶点c - Myc和MMP9的下调。STAT3过表达逆转了这些效应，证实了STAT3依赖性途径的参与。在小鼠异种移植模型中，卡拉醌A在体内抑制了肿瘤形成。分子对接分析进一步揭示了卡拉醌A与STAT3之间潜在的直接相互作用，支持了直接作用机制。这些发现表明，卡拉醌A通过靶向STAT3/c - Myc和STAT3/MMP9信号轴在胶质母细胞瘤中发挥强大的抗肿瘤作用，支持其作为GBM治疗的天然STAT3靶向剂的潜力。
