2. Academic Validation
  3. Deguelin inhibits the glioblastoma progression through suppressing CCL2/NFκB signaling pathway

Deguelin inhibits the glioblastoma progression through suppressing CCL2/NFκB signaling pathway

  • Neuropharmacology. 2024 Nov 15:259:110109. doi: 10.1016/j.neuropharm.2024.110109.
Yiming Qian 1,  Jianhong Dong 1,  Wei Zhang 1,  Xiumin Xue 1,  Zhenrong Xiong 1,  Weiquan Zeng 1,  Qian Wang 1,  Ziwei Fan 2,  Zhenxing Zuo 3,  Zhihui Huang 4,  Yuanyuan Jiang 5
Affiliations

Affiliations

  • 1 School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China.
  • 2 Department of Orthopedics (Spine Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, Zhejiang, China.
  • 3 Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
  • 4 School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China. Electronic address: huang0069@hznu.edu.cn.
  • 5 School of Pharmacy, Hangzhou Normal University, Hangzhou, 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, 311121, Zhejiang, China. Electronic address: jiangyuanyuan@hznu.edu.cn.
PMID: 39128581 DOI: 10.1016/j.neuropharm.2024.110109
Abstract

Glioblastoma multiforme (GBM) is the most common primary intracranial tumor with characteristics of high aggressiveness and poor prognosis. Deguelin, a component from the bark of Leguminosae Mundulea sericea (African plant), displays antiproliferative effects in some tumors, however, the inhibitory effect and mechanism of deguelin on GBM were still poorly understood. At first, we found that deguelin reduced the viability of GBM cells by causing cell cycle arrest in G2/M phase and inducing their Apoptosis. Secondly, deguelin inhibited the migration of GBM cells. Next, RNA-seq analysis identified that CCL2 (encoding chemokine CCL2) was downregulated significantly in deguelin-treated GBM cells. As reported, CCL2 promoted the cell growth, and CCL2 was associated with regulating NFκB signaling pathway, as well as involved in modulating tumor microenvironment (TME). Furthermore, we found that deguelin inactivated CCL2/NFκB signaling pathway, and exougous CCL2 could rescue the anti-inhibitory effect of deguelin on GBM cells via upregulating NFκB. Finally, we established a syngeneic intracranial orthotopic GBM model and found that deguelin regressed the tumor growth, contributed to an anti-tumorigenic TME and inhibited angiogenesis of GBM by suppressing CCL2/NFκB in vivo. Taken together, these results suggest the anti-GBM effect of deguelin via inhibiting CCL2/NFκB pathway, which may provide a new strategy for the treatment of GBM.

Keywords

CCL2/NFκB; Deguelin; Glioblastoma multiforme; Tumor microenvironment; Tumor-associated microglia/macrophages.

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