Molecular evaluation of quercetin effects in a murine model of giant cell tumor of bone: an in vivo pilot study.

Dalia Lizbeth Monroy-Quiroz, Alexandra Berenice Luna-Angulo, Brandon Eduardo Galicia-Canales, Laura Sánchez-Chapul, Olivia Hernández-González, María Del Rocío Aguilar-Gaytán, Mónica Guadalupe Santamaría-Olmedo, Alberto Hidalgo-Bravo, Beatriz Del Carmen Couder-García, Gabriel Lara-Hernández, Erendira Georgina Estrada-Villaseñor, Carlos Landa-Solís
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Abstract

Quercetin, a flavonoid derived from plant sources, has been extensively studied for its numerous biological properties, particularly its potential antitumor action against various malignant neoplasms. In our experience with a giant cell tumor of bone cell line (TIB-223), we demonstrated that quercetin has the ability to induce apoptosis via caspase-3. Therefore, this study aimed to evaluate molecular markers for apoptosis, necrosis, and cell proliferation in a murine model of giant cell tumor of bone, to determine whether the behavior reported for quercetin in 2D remains consistent in a 3D in vivo tumor model. Tumor constructs based on TIB-223 cells were implanted into athymic mice, and two weeks post-implantation, the mice were orally administered quercetin at a concentration of 100 mg/kg body weight once a day for two weeks. The control group received only 200 µL of the vehicle. Our results demonstrate the activation of two cell death pathways in the implanted tumors: apoptosis, via Caspase-8 to Caspase-3 activation, and necroptosis, via RIPK1. No significant effect on cell proliferation was observed, as PCNA expression remained unchanged. Our results suggest that quercetin may induce specific mechanisms of cell death without significantly altering cell proliferation in the tumor model induced in mice.

槲皮素在小鼠骨巨细胞瘤模型中作用的分子评价:一项体内初步研究。
槲皮素是一种从植物中提取的类黄酮,因其多种生物学特性,特别是其潜在的抗肿瘤作用而被广泛研究。在我们对骨细胞系巨细胞瘤(TIB-223)的研究中,我们证明槲皮素具有通过caspase-3诱导细胞凋亡的能力。因此,本研究旨在评估骨巨细胞瘤小鼠模型中凋亡、坏死和细胞增殖的分子标志物,以确定槲皮素在2D中报道的行为是否在3D体内肿瘤模型中保持一致。将基于TIB-223细胞的肿瘤构建物植入胸腺小鼠体内,植入2周后给予槲皮素100 mg/kg体重,每天1次,连续2周。对照组只接受200µL的载药。我们的研究结果表明,在植入肿瘤中激活了两种细胞死亡途径:通过Caspase-8到Caspase-3激活的细胞凋亡,以及通过RIPK1激活的坏死下垂。未观察到对细胞增殖的显著影响,PCNA表达保持不变。我们的研究结果表明,槲皮素可以诱导特定的细胞死亡机制,而不会显著改变小鼠肿瘤模型中的细胞增殖。
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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