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姜黄素诱导U-87 MG胶质母细胞瘤细胞的分子机制:来自全基因组表达谱分析的见解

Curcumin-Induced Molecular Mechanisms in U-87 MG Glioblastoma Cells: Insights from Global Gene Expression Profiling.

作者信息

Mashozhera Nicole Tendayi, Reddy Chinreddy Subramanyam, Ranasinghe Yevin Nenuka, Natarajan Purushothaman, Reddy Umesh K, Hankins Gerald

机构信息

Department of Biology, West Virginia State University, Institute, WV 25112, USA.

Department of Agriculture, Food, and Resource Sciences, University of Maryland Eastern Shore, Princess Anne, MD 21853, USA.

出版信息

Molecules. 2025 May 9;30(10):2108. doi: 10.3390/molecules30102108.

Abstract

Curcumin, a major phytochemical derived from Curcuma longa, has been shown to enhance the efficacy of chemotherapeutic agents such as doxorubicin, 5-fluorouracil, and cisplatin by overcoming drug resistance, making it a promising adjunct in the treatment of glioblastoma. However, the global gene-expression changes triggered by curcumin in glioblastoma remain underexplored. In this study, we investigated the effects of curcumin on human glioblastoma (U87 MG) cells, where it significantly reduced cell viability and proliferation in a dose- and time-dependent manner and induced apoptosis without affecting senescence. Transcriptomic analysis revealed 5036 differentially expressed genes, with pathway enrichment identifying 13 dysregulated cancer-associated pathways. Notably, curcumin modulated several key regulators involved in MAPK, Ras, TGF-β, Wnt, Cytokine, and TNF signaling pathways. Several apoptosis and cell cycle-associated genes, including PRKCG, GDF7, GDF9, GDF15, GDF5, FZD1, FZD2, FZD8, AIFM3, TP53AIP1, CRD14, NIBAN3, BOK, BCL2L10, BCL2L14, BNIPL, FASLG, GZMM, TNFSF10, TNFSF11, and TNFSF4, were significantly altered. Several pro-apoptotic and anti-BCL, cell-cycle-regulated genes were modulated following curcumin treatment, emphasizing its potential role in curcumin-mediated anti-tumor effects. This study provides insight into the molecular mechanisms underlying curcumin's action against glioblastoma.

摘要

姜黄素是从姜黄中提取的一种主要植物化学物质,已被证明可通过克服耐药性来增强阿霉素、5-氟尿嘧啶和顺铂等化疗药物的疗效,使其成为治疗胶质母细胞瘤的一种有前景的辅助药物。然而,姜黄素在胶质母细胞瘤中引发的全球基因表达变化仍未得到充分研究。在本研究中,我们调查了姜黄素对人胶质母细胞瘤(U87 MG)细胞的影响,结果显示它以剂量和时间依赖性方式显著降低细胞活力和增殖,并诱导细胞凋亡,而不影响细胞衰老。转录组分析揭示了5036个差异表达基因,通路富集分析确定了13条失调的癌症相关通路。值得注意的是,姜黄素调节了参与丝裂原活化蛋白激酶(MAPK)、Ras、转化生长因子-β(TGF-β)、Wnt、细胞因子和肿瘤坏死因子(TNF)信号通路的几个关键调节因子。包括蛋白激酶Cγ(PRKCG)、生长分化因子7(GDF7)、生长分化因子9(GDF9)、生长分化因子15(GDF15)、生长分化因子5(GDF5)、卷曲蛋白1(FZD1)、卷曲蛋白2(FZD2)、卷曲蛋白8(FZD8)、凋亡诱导因子线粒体相关3(AIFM3)、TP53凋亡诱导蛋白1(TP53AIP1)、CRD14、Niban蛋白3(NIBAN3)、Bcl-2同源拮抗剂/杀伤蛋白(BOK)、凋亡相关蛋白BCL2L10、BCL2L14、BNIPL、Fas配体(FASLG)、颗粒酶M(GZMM)、肿瘤坏死因子配体超家族成员10(TNFSF10)、肿瘤坏死因子配体超家族成员11(TNFSF11)和肿瘤坏死因子配体超家族成员4(TNFSF4)在内的几个凋亡和细胞周期相关基因发生了显著改变。姜黄素处理后,几个促凋亡和抗BCL、细胞周期调节基因受到调节,强调了其在姜黄素介导的抗肿瘤作用中的潜在作用。本研究深入探讨了姜黄素抗胶质母细胞瘤作用的分子机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b664/12113757/0073f9971188/molecules-30-02108-g001.jpg

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