2. Academic Validation
  3. Aloperine targets lysosomes to inhibit late autophagy and induces cell death through apoptosis and paraptosis in glioblastoma

Aloperine targets lysosomes to inhibit late autophagy and induces cell death through apoptosis and paraptosis in glioblastoma

  • Mol Biomed. 2023 Nov 17;4(1):42. doi: 10.1186/s43556-023-00155-x.
Ting Tang # 1 2,  Hui Liang # 2 3,  Wuting Wei 2,  Yanling Han 2,  Liang Cao 4,  Zixiang Cong 2,  Shiqiao Luo 5,  Handong Wang 6 7,  Meng-Liang Zhou 8
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Xuanwu Hospital Capital Medical University, Beijing, P.R. China.
  • 2 Department of Neurosurgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, P.R. China.
  • 3 Department of Neurosurgery, The First Affiliated Hospital, Guangxi Medical University, Nanning, P.R. China.
  • 4 Department of Medical Oncology, Affiliated Chuzhou Hospital of Anhui Medical University, The First People's Hospital of Chuzhou, Chuzhou, P.R. China.
  • 5 Department of Neurosurgery, Affiliated Jinling Hospital, Nanjing Medical University, Nanjing, P.R. China.
  • 6 Department of Neurosurgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, P.R. China. njhdwang@hotmail.com.
  • 7 Department of Neurosurgery, Benq Medical Center, Nanjing Medical University, Nanjing, China. njhdwang@hotmail.com.
  • 8 Department of Neurosurgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, P.R. China. mengliangzhou@yahoo.com.
  • # Contributed equally.
PMID: 37975957 DOI: 10.1186/s43556-023-00155-x
Abstract

Glioblastoma (GBM) is an aggressive intracranial tumour, and current chemotherapy regimens have limited efficacy. Aloperine (ALO), a natural alkaline compound, has shown potential as an antitumor agent. However, the effect of ALO against GBM remains unclear. This study aimed to investigate the function of ALO in treating GBM. U87, A172, and GL261 cell lines were used for in vitro experiments, and GL261 was also used to establish in vivo models. The results showed that ALO inhibited the proliferation of GBM cells by cell cycle arrest and Apoptosis. Furthermore, Autophagy was found to play a critical role, suggested by observation of autophagosomes under the transmission electron microscopy. It was discovered for the first time that ALO targeted lysosomes directly in glioma cells, tested by fluo-rescence-labelled ALO and organelle-localizing probes. In addition, ALO inhibited late Autophagy and induced Paraptosis in GBM, verified by classical gene expression changes in qPCR and western blotting. Also, ALO inhibited tumour growth and acted synergistically with temozolomide in intracranial glioma mice models in vivo. Our findings suggest that ALO targets lysosomes to inhibit late Autophagy in GBM, inducing cell cycle arrest, Paraptosis, and Apoptosis. ALO may therefore be a promising therapeutic agent for the treatment of GBM.

Keywords

Aloperine; Autophagy; Glioblastoma; Lysosome; Paraptosis.

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