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内源性大麻素是多形性胶质母细胞瘤增殖的潜在抑制剂。

Endocannabinoids are potential inhibitors of glioblastoma multiforme proliferation.

机构信息

School of Pharmacy, Wingate University, Wingate, NC 28174, USA; Applied Science and Technology Department, North Carolina State University of Agriculture and Technology, Greensboro, NC 27411, USA.

College of Nursing, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

出版信息

J Integr Med. 2023 Mar;21(2):120-129. doi: 10.1016/j.joim.2023.01.005. Epub 2023 Feb 2.

Abstract

Globally, it is evident that glioblastoma multiforme (GBM) is an aggressive malignant cancer with a high mortality rate and no effective treatment options. Glioblastoma is classified as the stage-four progression of a glioma tumor, and its diagnosis results in a shortened life expectancy. Treatment options for GBM include chemotherapy, immunotherapy, surgical intervention, and conventional pharmacotherapy; however, at best, they extend the patient's life by a maximum of 5 years. GBMs are considered incurable due to their high recurrence rate, despite various aggressive therapeutic approaches which can have many serious adverse effects. Ceramides, classified as endocannabinoids, offer a promising novel therapeutic approach for GBM. Endocannabinoids may enhance the apoptosis of GBM cells but have no effect on normal healthy neural cells. Cannabinoids promote atypical protein kinase C, deactivate fatty acid amide hydrolase enzymes, and activate transient receptor potential vanilloid 1 (TRPV1) and TRPV2 to induce pro-apoptotic signaling pathways without increasing endogenous cannabinoids. In previous in vivo studies, endocannabinoids, chemically classified as amide formations of oleic and palmitic acids, have been shown to increase the pro-apoptotic activity of human cancer cells and inhibit cell migration and angiogenesis. This review focuses on the biological synthesis and pharmacology of endogenous cannabinoids for the enhancement of cancer cell apoptosis, which have potential as a novel therapy for GBM. Please cite this article as: Duzan A, Reinken D, McGomery TL, Ferencz N, Plummer JM, Basti MM. Endocannabinoids are potential inhibitors of glioblastoma multiforme proliferation. J Integr Med. 2023; 21(2): 120-128.

摘要

从全球范围来看,胶质母细胞瘤(GBM)显然是一种具有高死亡率且没有有效治疗方法的侵袭性恶性癌症。GBM 被归类为胶质瘤肿瘤的四级进展,其诊断结果导致预期寿命缩短。GBM 的治疗选择包括化疗、免疫疗法、手术干预和常规药物治疗;然而,这些治疗方法最多只能将患者的生命延长 5 年。尽管采用了各种激进的治疗方法,但由于复发率高,GBM 仍被认为无法治愈,这些方法可能会产生许多严重的不良反应。神经酰胺被归类为内源性大麻素,为 GBM 提供了一种有前途的新型治疗方法。内源性大麻素可能增强 GBM 细胞的凋亡,但对正常健康的神经细胞没有影响。大麻素促进非典型蛋白激酶 C 的激活、使脂肪酸酰胺水解酶失活,并激活瞬时受体电位香草素 1(TRPV1)和 TRPV2,从而诱导促凋亡信号通路,而不会增加内源性大麻素。在之前的体内研究中,化学分类为油酸和棕榈酸酰胺形成的内源性大麻素已被证明可增加人类癌细胞的促凋亡活性,并抑制细胞迁移和血管生成。本综述重点介绍内源性大麻素的生物合成和药理学,以增强癌细胞凋亡,这可能成为 GBM 的一种新疗法。请引用本文作为:Duzan A, Reinken D, McGomery TL, Ferencz N, Plummer JM, Basti MM. Endocannabinoids are potential inhibitors of glioblastoma multiforme proliferation. J Integr Med. 2023; 21(2): 120-128.

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