Piperlongumine induces meningioma cell death via the ROS-mediated endoplasmic reticulum stress and the alteration of the ubiquitin-proteasome system.

IF 3.1 2区医学 Q2 CLINICAL NEUROLOGY

Journal of Neuro-Oncology Pub Date : 2025-12-01 Epub Date: 2025-09-15 DOI:10.1007/s11060-025-05219-2

Nopporn Naewwan, Krajang Talabnin, Thanawat Trasaktaweesakul, Phattrara Khuansonthi, Pundit Asavaritikrai, Pitchanun Jaturutthaweechot, Chutima Talabnin

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引用次数: 0

Abstract

Purpose: Meningiomas, the most common primary tumors of the central nervous system, are curable by surgical resection and radiotherapy. However, systemic therapeutic chemotherapy for meningiomas has not existed. Piperlongumine (PL), a natural alkaloid extracted from the long pepper (Piper longum), has emerged as a promising candidate for cancer treatment due to its multimodal anti-cancer effects. However, the effects of PL in meningiomas are limited.

Methods: We examined the anti-cancer effect of PL in vitro using primary benign meningioma cells and malignant meningioma cells. The underlying mechanism of PL in meningiomas was investigated through gene expression experiments at both mRNA and protein levels.

Results: PL inhibited meningioma cell growth, evidenced by inducing G2/M phase arrest via the up-regulation of cell cycle regulators including TP53 and CDKN1A/p21 and enhancing cell apoptosis via the up-regulation of cleaved caspase 3 and cleaved PARP1. PL-induced meningioma cell death was triggered via the activation of intracellular reactive oxygen species production leading to endoplasmic reticulum stress and the alteration of ubiquitin-proteasome system resulting in the accumulation of poly-ubiquitinated proteins.

Conclusion: The present study indicates that PL has anti-cancer effect against meningiomas.

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胡椒明通过ros介导的内质网应激和泛素-蛋白酶体系统的改变诱导脑膜瘤细胞死亡。

目的：脑膜瘤是最常见的中枢神经系统原发肿瘤，可通过手术切除和放疗治愈。然而，目前还没有针对脑膜瘤的系统治疗性化疗。胡椒明（Piperlongumine， PL）是一种从辣椒（Piper longum）中提取的天然生物碱，由于其多种模式的抗癌作用而成为治疗癌症的有希望的候选者。然而，PL在脑膜瘤中的作用有限。方法：以原发性良性脑膜瘤细胞和恶性脑膜瘤细胞为实验对象，观察其体外抗癌作用。通过mRNA和蛋白水平的基因表达实验，探讨了PL在脑膜瘤中的潜在机制。结果：PL抑制脑膜瘤细胞生长，通过上调TP53和CDKN1A/p21等细胞周期调节因子诱导G2/M期阻滞，通过上调裂解caspase 3和裂解PARP1促进细胞凋亡。pl诱导的脑膜瘤细胞死亡是通过激活细胞内活性氧产生导致内质网应激和改变泛素-蛋白酶体系统导致多泛素化蛋白积累而触发的。结论：枸杞多糖对脑膜瘤具有抗癌作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Neuro-Oncology 医学-临床神经学

CiteScore

6.60

自引率

7.70%

发文量

277

审稿时长

3.3 months

期刊介绍： The Journal of Neuro-Oncology is a multi-disciplinary journal encompassing basic, applied, and clinical investigations in all research areas as they relate to cancer and the central nervous system. It provides a single forum for communication among neurologists, neurosurgeons, radiotherapists, medical oncologists, neuropathologists, neurodiagnosticians, and laboratory-based oncologists conducting relevant research. The Journal of Neuro-Oncology does not seek to isolate the field, but rather to focus the efforts of many disciplines in one publication through a format which pulls together these diverse interests. More than any other field of oncology, cancer of the central nervous system requires multi-disciplinary approaches. To alleviate having to scan dozens of journals of cell biology, pathology, laboratory and clinical endeavours, JNO is a periodical in which current, high-quality, relevant research in all aspects of neuro-oncology may be found.