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

Abstract 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 molec...

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Main Authors: Wen-Chi Hsieh, Chun-Yu Lin, Hsuan‐Cheng Wu, Huang-Wei Lo, Chiung-Yuan Ko, Jian-Ying Chuang, Tsung-I. Hsu, Tsui-Hwa Tseng, Teng-Wei Huang, Shao-Ming Wang
Format: Article
Language:English
Published: Springer 2025-08-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-03279-4
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author Wen-Chi Hsieh
Chun-Yu Lin
Hsuan‐Cheng Wu
Huang-Wei Lo
Chiung-Yuan Ko
Jian-Ying Chuang
Tsung-I. Hsu
Tsui-Hwa Tseng
Teng-Wei Huang
Shao-Ming Wang
author_facet Wen-Chi Hsieh
Chun-Yu Lin
Hsuan‐Cheng Wu
Huang-Wei Lo
Chiung-Yuan Ko
Jian-Ying Chuang
Tsung-I. Hsu
Tsui-Hwa Tseng
Teng-Wei Huang
Shao-Ming Wang
author_sort Wen-Chi Hsieh
collection DOAJ
description Abstract 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. Graphical abstract
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spelling doaj-art-e8bbc0cba6324424b62eaea78744dfbb2025-08-20T03:43:11ZengSpringerDiscover Oncology2730-60112025-08-0116111910.1007/s12672-025-03279-4Calanquinone A suppresses glioma progression via STAT3-mediated regulation of c-Myc and MMP9Wen-Chi Hsieh0Chun-Yu Lin1Hsuan‐Cheng Wu2Huang-Wei Lo3Chiung-Yuan Ko4Jian-Ying Chuang5Tsung-I. Hsu6Tsui-Hwa Tseng7Teng-Wei Huang8Shao-Ming Wang9Neuroscience and Brain Disease Center, China Medical UniversityNeuroscience and Brain Disease Center, China Medical UniversityNeuroscience and Brain Disease Center, China Medical UniversityNeuroscience and Brain Disease Center, China Medical UniversitySchool of Medicine, College of Medicine, National Sun Yat-sen UniversityPh.D. Program in Medical Neuroscience, College of Medical Science and Technology, Taipei Medical UniversityPh.D. Program in Medical Neuroscience, College of Medical Science and Technology, Taipei Medical UniversityDepartment of Medical Applied Chemistry, Chung Shan Medical UniversityNeuroscience and Brain Disease Center, China Medical UniversityNeuroscience and Brain Disease Center, China Medical UniversityAbstract 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. Graphical abstracthttps://doi.org/10.1007/s12672-025-03279-4Calanthe arisanensisCalanquinone aPhytochemicalGlioblastoma multiformeSTAT3Migration
spellingShingle Wen-Chi Hsieh
Chun-Yu Lin
Hsuan‐Cheng Wu
Huang-Wei Lo
Chiung-Yuan Ko
Jian-Ying Chuang
Tsung-I. Hsu
Tsui-Hwa Tseng
Teng-Wei Huang
Shao-Ming Wang
Calanquinone A suppresses glioma progression via STAT3-mediated regulation of c-Myc and MMP9
Discover Oncology
Calanthe arisanensis
Calanquinone a
Phytochemical
Glioblastoma multiforme
STAT3
Migration
title Calanquinone A suppresses glioma progression via STAT3-mediated regulation of c-Myc and MMP9
title_full Calanquinone A suppresses glioma progression via STAT3-mediated regulation of c-Myc and MMP9
title_fullStr Calanquinone A suppresses glioma progression via STAT3-mediated regulation of c-Myc and MMP9
title_full_unstemmed Calanquinone A suppresses glioma progression via STAT3-mediated regulation of c-Myc and MMP9
title_short Calanquinone A suppresses glioma progression via STAT3-mediated regulation of c-Myc and MMP9
title_sort calanquinone a suppresses glioma progression via stat3 mediated regulation of c myc and mmp9
topic Calanthe arisanensis
Calanquinone a
Phytochemical
Glioblastoma multiforme
STAT3
Migration
url https://doi.org/10.1007/s12672-025-03279-4
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