Calanquinone A suppresses glioma progression via STAT3-mediated regulation of c-Myc and MMP9.

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.