2. Academic Validation
  3. Lupeol induces apoptosis of glioma cells via governing ubiquitination-mediated SPARC turnover

Lupeol induces apoptosis of glioma cells via governing ubiquitination-mediated SPARC turnover

  • Tissue Cell. 2025 Jul 8:97:103039. doi: 10.1016/j.tice.2025.103039.
Yiting Wei 1,  Yulin Wan 2,  Shilong Duan 3,  Qiongyao Hu 4,  Nanjian Xu 5
Affiliations

Affiliations

  • 1 Ningbo Key Laboratory of Nervous System and Brain Function, Department of Neurosurgery, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, China.
  • 2 Department of Neurosurgery, Ningbo Seventh Hospital, Ningbo, Zhejiang, China.
  • 3 Department of Rehabilitation, Ningbo Zhenhai Longsai Hospital, Ningbo, Zhejiang, China.
  • 4 Department of Scientific Research and Education, Zhenhai District Hospital of Traditional Chinese Medicine, Ningbo, Zhejiang, China.
  • 5 Spine Surgery Center, Ningbo No.6 Hospital, Ningbo City, Zhejiang Province, PR China; Ningbo Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation, Ningbo, Zhejiang, China. Electronic address: nj3152079@163.com.
PMID: 40779907 DOI: 10.1016/j.tice.2025.103039
Abstract

Glioblastoma multiforme (GBM) remains a lethal malignancy with limited therapeutic options due to its aggressive progression and resistance to Apoptosis. SPARC (secreted protein acidic and rich in cysteine), a multifunctional glycoprotein implicated in glioma survival and chemoresistance, is stabilized by deubiquitinating Enzymes (DUBs), yet the regulatory mechanisms driving its turnover are poorly defined. Lupeol, a natural triterpenoid, exhibits Anticancer potential, but its effects on glioma and underlying molecular mechanisms remain elusive. Here, we demonstrate that lupeol induces Apoptosis in glioma cells by targeting ubiquitination-mediated SPARC degradation. Mechanistically, lupeol enhanced SPARC polyubiquitination by disrupting its interaction with Ubiquitin-Specific Protease 14 (USP14), a DUB that antagonizes proteasomal degradation of SPARC. These findings unveil a novel mechanism by which lupeol triggers Apoptosis through USP14-dependent SPARC ubiquitination and degradation, highlighting the therapeutic potential of targeting the USP14-SPARC axis in glioma treatment. This study provides the first evidence linking lupeol's Anticancer activity to ubiquitination-regulated protein turnover, offering insights for developing SPARC-directed therapies against gliomas.

Keywords

Glioma; Lupeol; SPARC; USP14; Ubiquitination.

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