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大麻素富集产物对骨髓瘤细胞功能的抑制作用与端粒和 TP53 的调节有关。

Inhibition of Myeloma Cell Function by Cannabinoid-Enriched Product Associated With Regulation of Telomere and TP53.

机构信息

New York Medical College, Valhalla, NY, USA.

General Nutraceutical Technology LLC, Elmsford, NY, USA.

出版信息

Integr Cancer Ther. 2024 Jan-Dec;23:15347354241267979. doi: 10.1177/15347354241267979.

Abstract

Multiple myeloma is a hematological cancer caused by the uncontrolled proliferation of abnormal plasma cells in the bone marrow, leading to excessive immunoglobulin production. Our study aimed to examine the anticancer properties of BRF1A, a cannabinoid (CBD)-enriched product, on 2 myeloma cell lines: U266 and ARH-7. We treated U266 and ARH-77 myeloma cells with varying doses of BRF1A and measured the production of IgE and IgG antibodies using ELISA. Cell viability was assessed using trypan blue and CCK-8 assays. We measured the expression of genes related to the production of IgE and IgG antibodies, IgEH, and IgGH. We determined its effect on the expression of telomerase and its phosphorylated form as an indicator of telomere stabilization. Furthermore, we determined its effect on other cancer-related targets such as NF-ĸB, c-Myc, and TP53 in U266 cells using reverse transcription polymerase chain reaction (RT-PCR) and western blotting. BRF1A reduced myeloma cell IgE and IgG production in a time and dose-dependent manner. It also suppressed the expression of p-IκBα, p-NFκB (p65), and total NFκB protein, as well as XBP1u and XBP1s. It increased the gene and protein expression of telomere and hTERT and significantly increased cancer suppressor TP53 gene and p53 protein expression. Additionally, BRF1A decreased the c-Myc gene and protein expression. Our study has shown that a CBD-enriched product can reduce the growth of myeloma cells by suppressing the critical functions of IgE- and IgG-producing cells. This study could help bridge the gap in understanding how cannabinoid-containing products affect cancer, aging, telomere, and cancer-suppressor gene activity.

摘要

多发性骨髓瘤是一种血液系统癌症,由骨髓中异常浆细胞的不受控制增殖引起,导致免疫球蛋白过度产生。我们的研究旨在研究 BRF1A(一种富含大麻素(CBD)的产品)对 2 种骨髓瘤细胞系 U266 和 ARH-7 的抗癌特性。我们用不同剂量的 BRF1A 处理 U266 和 ARH-77 骨髓瘤细胞,并使用 ELISA 测量 IgE 和 IgG 抗体的产生。使用台盼蓝和 CCK-8 测定法评估细胞活力。我们测量了与 IgE 和 IgG 抗体、IgEH 和 IgGH 产生相关的基因的表达。我们确定了它对端粒酶及其磷酸化形式表达的影响,作为端粒稳定的指标。此外,我们使用逆转录聚合酶链反应 (RT-PCR) 和蛋白质印迹法在 U266 细胞中确定了它对其他与癌症相关的靶标如 NF-ĸB、c-Myc 和 TP53 的影响。BRF1A 以时间和剂量依赖的方式减少骨髓瘤细胞 IgE 和 IgG 的产生。它还抑制了 p-IκBα、p-NFκB(p65)和总 NFκB 蛋白以及 XBP1u 和 XBP1s 的表达。它增加了端粒和 hTERT 的基因和蛋白表达,并显著增加了抑癌基因 TP53 的基因和 p53 蛋白的表达。此外,BRF1A 降低了 c-Myc 基因和蛋白的表达。我们的研究表明,富含 CBD 的产品可以通过抑制 IgE 和 IgG 产生细胞的关键功能来减少骨髓瘤细胞的生长。这项研究有助于弥合对大麻素类产品如何影响癌症、衰老、端粒和抑癌基因活性的理解差距。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/120e/11406604/9c5759393c93/10.1177_15347354241267979-fig1.jpg

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