Kłósek Małgorzata, Kurek-Górecka Anna, Balwierz Radosław, Pietsz Grażyna, Czuba Zenon P
Department of Microbiology and Immunology, Faculty of Medical Sciences, Medical University of Silesia in Katowice, Jordana 19, 41-808 Zabrze, Poland.
Institute of Chemistry, University of Opole, Oleska 48, 45-052 Opole, Poland.
Molecules. 2025 Jul 17;30(14):3008. doi: 10.3390/molecules30143008.
Tissue hypoxia is commonly observed in head cancers and contributes to both molecular and functional changes in tumour cells. It is known to stimulate erythropoiesis, angiogenesis, and metabolic alterations within tumour cells. Glioblastoma, a type of brain tumour, is characterized by rapid proliferation and aggressive growth. Recent studies have indicated that natural products may hold potential as components of cancer therapy. Among these, Polish propolis and its active compound, quercetin, have demonstrated promising anti-cancer properties. The aim of this study was to evaluate the concentrations of selected cytokines-specifically IL-6, IL-9, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF-BB), interferon gamma-induced protein 10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1)-produced by astrocytes of the CCF-STTG1 cell line. The cytotoxic effects of ethanolic extract of propolis (EEP) and quercetin were assessed using the MTT assay. Astrocytes were stimulated with lipopolysaccharide (LPS, 200 ng/mL) and/or IFN-α (100 U/mL), followed by treatment with EEP or quercetin (25-50 µg/mL) under hypoxic conditions for two hours. Cytokine concentrations were measured using the xMAP Luminex Multiplex Immunoassay and the Multiplex Bead-Based Cytokine Kit. Our study demonstrated that Polish propolis and its component quercetin modulate the tumour microenvironment in vitro, primarily by altering the levels of specific cytokines. The HCA analysis revealed that IL-6 and MCP-1 formed a distinct cluster at the highest linkage distance (approximately 100% of Dmax), suggesting that their expression patterns are significantly different from those of the other cytokines and that they are more similar to each other than to the rest. PCA analysis showed that EEP-PL (50 μg/mL) with IFN-α and EEP-PL (50 μg/mL) with LPS exert similar activities on cytokine secretion by astrocytes. Similar effects were demonstrated for EEP-PL 50 μg/mL + LPS + IFN-α, EEP-PL 25 μg/mL + IFN-α and EEP-PL 25 μg/mL + LPS + IFN-α. Our findings suggest that Polish propolis and quercetin may serve as promising natural agents to support the treatment of stage IV malignant astrocytoma. Nonetheless, further research is needed to confirm these results.
组织缺氧在头颈部癌症中普遍存在，并导致肿瘤细胞发生分子和功能变化。已知它会刺激肿瘤细胞内的红细胞生成、血管生成和代谢改变。胶质母细胞瘤是一种脑肿瘤，其特征是快速增殖和侵袭性生长。最近的研究表明，天然产物可能具有作为癌症治疗成分的潜力。其中，波兰蜂胶及其活性化合物槲皮素已显示出有前景的抗癌特性。本研究的目的是评估CCF-STTG1细胞系星形胶质细胞产生的特定细胞因子——具体为白细胞介素-6（IL-6）、白细胞介素-9（IL-9）、血管内皮生长因子（VEGF）、血小板衍生生长因子（PDGF-BB）、干扰素γ诱导蛋白10（IP-10）和单核细胞趋化蛋白-1（MCP-1）的浓度。使用MTT法评估蜂胶乙醇提取物（EEP）和槲皮素的细胞毒性作用。用脂多糖（LPS，200 ng/mL）和/或干扰素-α（IFN-α，100 U/mL）刺激星形胶质细胞，然后在缺氧条件下用EEP或槲皮素（25 - 50 μg/mL）处理两小时。使用xMAP Luminex多重免疫测定法和基于微珠的多重细胞因子试剂盒测量细胞因子浓度。我们的研究表明，波兰蜂胶及其成分槲皮素主要通过改变特定细胞因子的水平在体外调节肿瘤微环境。热凝聚分析（HCA）显示，IL-6和MCP-1在最高连锁距离（约为最大距离Dmax的100%）处形成一个独特的簇，这表明它们的表达模式与其他细胞因子的表达模式显著不同，且它们彼此之间比与其他细胞因子更相似。主成分分析（PCA）表明，含IFN-α的EEP-PL（50 μg/mL）和含LPS的EEP-PL（50 μg/mL）对星形胶质细胞分泌细胞因子具有相似的作用。EEP-PL 50 μg/mL + LPS + IFN-α、EEP-PL 25 μg/mL + IFN-α和EEP-PL 25 μg/mL + LPS + IFN-α也显示出类似的效果。我们的研究结果表明，波兰蜂胶和槲皮素可能是支持治疗IV期恶性星形细胞瘤的有前景的天然药物。尽管如此，仍需要进一步研究来证实这些结果。
