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

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机构： [1]Department of Neurosurgery, Xuanwu Hospital Capital Medical University, Bejing, P.R. China [2]Department of Neurosurgery, Affliated Jinling Hospital, Medical School . of Nanjing University, Nanjing, P.R. China [3]Department of Neurosurgery, The First Affliated Hospital, Guangxi Medical University, Nanning, P.R. China [4]Department of Medical Oncology, Affliated Chuzhou Hospital of Anhui Medical University, The First People's Hospital of Chuzhou, Chuzhou, P.R. China [5]Department of Neurosurgery, Affliated Jinling Hospital, Nanjing Medical University, Nanjing, P.R. China [6]Department of Neurosurgery, Benq Medical Center, Nanjing Medical University, Nanjing, China

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关键词： Aloperine Glioblastoma Autophagy Lysosome Paraptosis

摘要：

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.© 2023. The Author(s).

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大类 | 2 区医学

小类 | 2 区生化与分子生物学 2 区细胞生物学 2 区医学：研究与实验

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最新[2023]版：

Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Q1 CELL BIOLOGY Q1 MEDICINE, RESEARCH & EXPERIMENTAL

影响因子： 6.3 最新[2023版] 6.2 最新五年平均 0 出版当年[2021版] 0 出版当年五年平均 0 出版前一年[2020版] 4 出版后一年[2022版]

第一作者：

第一作者机构： [1]Department of Neurosurgery, Xuanwu Hospital Capital Medical University, Bejing, P.R. China [2]Department of Neurosurgery, Affliated Jinling Hospital, Medical School . of Nanjing University, Nanjing, P.R. China

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通讯作者：

通讯机构： [2]Department of Neurosurgery, Affliated Jinling Hospital, Medical School . of Nanjing University, Nanjing, P.R. China [6]Department of Neurosurgery, Benq Medical Center, Nanjing Medical University, Nanjing, China

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

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