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甲醇提取物诱导 G 细胞周期停滞和凋亡并抑制神经胶质瘤细胞转移。

Methanolic Extract of Induces G Cell Cycle Arrest and Apoptosis and Inhibits Metastasis of Glioma Cells.

机构信息

School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 80756, Taiwan.

Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan.

出版信息

Nutrients. 2024 Sep 26;16(19):3254. doi: 10.3390/nu16193254.

DOI:10.3390/nu16193254
PMID:39408228
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11478387/
Abstract

BACKGROUND

Glioblastoma multiforme (GBM) is among the most aggressive and challenging brain tumors, with limited treatment options. , a traditional Chinese medicine, has shown promise due to its bioactive components. This study investigates the anti-glioma effects of a methanolic extract of (CF-ME) in GBM cell lines.

METHODS

The effects of CF-ME and its index compounds (caffeic acid, cimifugin, ferulic acid, and isoferulic acid) on GBM cell viability were assessed using MTT assays on U87 MG, A172, and T98G cell lines. The ability of CF-ME to induce cell cycle arrest, apoptosis, and autophagy and inhibit metastasis was evaluated using flow cytometry, Western blotting, and functional assays. Additionally, the synergistic potential of CF-ME with temozolomide (TMZ) was explored.

RESULTS

CF-ME significantly reduced GBM cell viability in a dose- and time-dependent manner, induced G1 phase cell cycle arrest, promoted apoptosis via caspase activation, and triggered autophagy. CF-ME also inhibited GBM cell invasion, migration, and adhesion, likely by modulating epithelial-mesenchymal transition (EMT) markers. Combined with TMZ, CF-ME further enhanced reduced GBM cell viability, suggesting a potential synergistic effect. However, the individual index compounds of CF-ME exhibited only modest inhibitory effects, indicating that the full anti-glioma activity may result from the synergistic interactions among its components.

CONCLUSIONS

CF-ME exhibited potent anti-glioma activity through multiple mechanisms, including cell cycle arrest, apoptosis, autophagy, and the inhibition of metastasis. Combining CF-ME with TMZ further enhanced its therapeutic potential, making it a promising candidate for adjuvant therapy in glioblastoma treatment.

摘要

背景

多形性胶质母细胞瘤(GBM)是最具侵袭性和挑战性的脑肿瘤之一,治疗选择有限。作为一种传统中药,因其生物活性成分而显示出潜力。本研究探讨了一种 (CF-ME)的甲醇提取物对 GBM 细胞系的抗神经胶质瘤作用。

方法

采用 MTT 法检测 CF-ME 及其指标化合物(咖啡酸、苦参素、阿魏酸和异阿魏酸)对 U87 MG、A172 和 T98G 细胞系的影响,评估 CF-ME 诱导细胞周期停滞、凋亡和自噬以及抑制转移的能力。通过流式细胞术、Western blot 和功能测定评估 CF-ME 与替莫唑胺(TMZ)的协同潜力。

结果

CF-ME 显著降低 GBM 细胞活力,呈剂量和时间依赖性,诱导 G1 期细胞周期停滞,通过半胱天冬酶激活促进细胞凋亡,并触发自噬。CF-ME 还抑制 GBM 细胞侵袭、迁移和黏附,可能通过调节上皮-间充质转化(EMT)标志物。与 TMZ 联合使用时,CF-ME 进一步增强了降低的 GBM 细胞活力,表明存在潜在的协同作用。然而,CF-ME 的单个指标化合物仅表现出适度的抑制作用,表明其全部抗神经胶质瘤活性可能是由于其成分之间的协同相互作用所致。

结论

CF-ME 通过多种机制表现出强大的抗神经胶质瘤活性,包括细胞周期停滞、凋亡、自噬和转移抑制。CF-ME 与 TMZ 联合使用进一步增强了其治疗潜力,使其成为胶质母细胞瘤治疗中辅助治疗的有前途的候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1b0/11478387/a0ae314b58c9/nutrients-16-03254-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1b0/11478387/3ded2add6cd9/nutrients-16-03254-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1b0/11478387/3a86eb6249f0/nutrients-16-03254-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1b0/11478387/3a1ef00c36a7/nutrients-16-03254-g003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1b0/11478387/2522c152332d/nutrients-16-03254-g004a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1b0/11478387/45c3f46c97b3/nutrients-16-03254-g005a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1b0/11478387/717412e2aaac/nutrients-16-03254-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1b0/11478387/b56ce6022142/nutrients-16-03254-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1b0/11478387/a0ae314b58c9/nutrients-16-03254-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1b0/11478387/3ded2add6cd9/nutrients-16-03254-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1b0/11478387/3a86eb6249f0/nutrients-16-03254-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1b0/11478387/3a1ef00c36a7/nutrients-16-03254-g003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1b0/11478387/2522c152332d/nutrients-16-03254-g004a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1b0/11478387/45c3f46c97b3/nutrients-16-03254-g005a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1b0/11478387/717412e2aaac/nutrients-16-03254-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1b0/11478387/b56ce6022142/nutrients-16-03254-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c1b0/11478387/a0ae314b58c9/nutrients-16-03254-g008.jpg

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