2. Academic Validation
  3. Isocucurbitacin B inhibits gliomas through the promotion of anoikis by targeting caveolin 1

Isocucurbitacin B inhibits gliomas through the promotion of anoikis by targeting caveolin 1

  • Cancer Lett. 2025 Oct 1:629:217873. doi: 10.1016/j.canlet.2025.217873.
Mingyu Han 1,  Jianning Yang 2,  Pingting Chen 3,  Sui Li 4,  Hailin Tang 5,  Huali Fan 2,  Yuhan Wang 2,  Xue Li 2,  Weiwei Pan 6,  Vasili Koutouratsas 7,  Zijin Zhao 8,  Fu Peng 9
Affiliations

Affiliations

  • 1 West China School of Pharmacy, Sichuan University, Chengdu, 610041, China; Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410043, China; National Clinical Research Center for Geriatric Disorders (Xiangya Hospital), Central South University, 410031, Changsha, China.
  • 2 West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
  • 3 West China School of Pharmacy, Sichuan University, Chengdu, 610041, China; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
  • 4 West China School of Pharmacy, Sichuan University, Chengdu, 610041, China; Waigaoqiao Free Trade Zone, WuXi Biologics, Shanghai, 214122, China.
  • 5 State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China.
  • 6 Department of Cell Biology, College of Medicine, Jiaxing University, 118 Jiahang Road, Jiaxing, 314001, China.
  • 7 College of Pharmacy and Health Sciences, St. John's University, Queens, New York, 11439, USA.
  • 8 Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, 410043, China; National Clinical Research Center for Geriatric Disorders (Xiangya Hospital), Central South University, 410031, Changsha, China. Electronic address: [email protected].
  • 9 West China School of Pharmacy, Sichuan University, Chengdu, 610041, China; Department of Pharmacology, Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, Sichuan University, Chengdu, 610041, China. Electronic address: [email protected].
PMID: 40516904 DOI: 10.1016/j.canlet.2025.217873
Abstract

Gliomas, known for their aggressive nature, high recurrence rates, and resistance to conventional therapies, require the development of novel treatment strategies. This study emphasizes the critical role of caveolin 1 (CAV1) in glioma progression and highlights the potent anti-glioma effects of isocucurbitacin B. The compound effectively inhibits glioma cell proliferation, invasion, migration, and epithelial-mesenchymal transition, while also inducing G2/M phase arrest and promoting Apoptosis. Further analysis revealed that isocucurbitacin B promotes anoikis, a form of cell death induced by detachment, by downregulating CAV1. Notably, isocucurbitacin B directly binds to CAV1, confirmed by cellular thermal shift assays and microscale thermophoresis, positioning CAV1 as a key therapeutic target. Additionally, isocucurbitacin B activates the BKCa Calcium Channel, resulting in increased intracellular CA2+ and reduced pH, establishing a novel connection between calcium dynamics and anoikis. Overexpression of CAV1 inhibited anoikis, blocking Apoptosis and promoting migration, while decreased CAV1 expression facilitated anoikis and significantly reduced glioma cell proliferation and motility. In vivo experiments using zebrafish patient-derived xenografts and orthotopic glioblastoma models further demonstrated that isocucurbitacin B effectively suppresses tumor growth by downregulating CAV1. These findings underscore the multifaceted anti-glioma potential of isocucurbitacin B and highlight CAV1 as a crucial mediator of anoikis and a promising therapeutic target in glioma treatment.

Keywords

Anoikis; CETSA; Caveolin 1; Glioblastoma; Isocucurbitacin B; Orthotopic glioma mouse model; PDX model.

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