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ITF2357 induces cell cycle arrest and apoptosis of meningioma cells via the PI3K-Akt pathway

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Abstract

As a type of central nervous system tumor, meningioma usually compresses the nerve center due to its local expansion, further causing neurological deficits. However, there are limited therapeutic approaches for meningiomas. ITF2357, a potent class I and II histone deacetylase inhibitor (HDACi), has been shown to inhibit cell proliferation, promote apoptosis, and block the cell cycle in various sarcoma cells, including glioblastoma and peripheral T-cell lymphoma. Here, we investigated the potential role of ITF2357 on meningioma cancer cells (IOMM-Lee cells). First, we demonstrated that the half-maximal inhibitory concentration (IC50) of ITF2357 was 1.842 μM by MTT assay. In addition, ITF2357 effectively inhibited the proliferation and colonization ability of IOMM-Lee cells. Flow cytometry analysis showed that ITF2357 induced G0/G1 and G2/M phase cell cycle arrest and cell apoptosis. Mechanically, the RNA sequencing data revealed that ITF2357 could affect the PI3K-Akt signaling pathway and the cell cycle progression. Furthermore, the expression levels of Akt, PI3K, p-Akt, and p-PI3K were determined by western blotting. Collectively, our data revealed that ITF2357 induces G0 G1 and G2/M phase arrest and apoptosis by inhibiting hyperactivation of the PI3K-Akt pathway, ultimately inhibiting cell viability and proliferation of meningioma cells, which developed a new approach to the treatment of meningioma.

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Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81900287), Tianshan Youth Foundation of Xinjiang (Grant No. 2019Q066).

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  1. Lingying Zhang and Chengyu Li have contributed equally to this work.

Authors and Affiliations

  1. Xinjiang Key Laboratory of Biological Resources and Gentic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, 830046, China

    Lingying Zhang, Chengyu Li,  Marhaba·Aziz, Rongxin Zhu & Zeyidan Jiapaer

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  1. Lingying Zhang
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  2. Chengyu Li
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  3. Marhaba·Aziz
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Contributions

LZ and CL: contributed equally to this work, including study conception and design, performing the experiments, data analysis, and manuscript writing. MA and RZ: were involved in manuscript preparation. RZ: contributed to the microarray data analysis. ZJ: designed and supervised the project and provided financial support and manuscript writing.

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Correspondence to Zeyidan Jiapaer.

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Zhang, L., Li, C., Marhaba·Aziz et al. ITF2357 induces cell cycle arrest and apoptosis of meningioma cells via the PI3K-Akt pathway. Med Oncol 40, 21 (2023). https://doi.org/10.1007/s12032-022-01883-w

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