Altin-Celik Pınar, Derya-Andeden Muazzez, Eciroglu-Sarban Hamiyet, Donmez-Altuntas Hamiyet
Department of Medical Biology, Medical Faculty, Erciyes University, 38030, Kayseri, Türkiye.
Vocational School of Health Services, Alanya Alaaddin Keykubat University, Antalya, Türkiye.
Med Oncol. 2025 Jul 30;42(9):394. doi: 10.1007/s12032-025-02963-3.
Neuroblastoma is a complex and heterogeneous pediatric malignancy. Treatment options for neuroblastoma include surgery, chemotherapy, radiotherapy, autologous stem cell transplantation, and emerging immunotherapies. However, these approaches often coincide with oxidative stress, highlighting the potential role of natural antioxidants in chemoprevention and chemotherapy. Honey has long been recognized for its medicinal properties, including antimicrobial, anti-inflammatory, and antioxidant effects. Pervari honey (PH), produced by bees that forage on a diverse array of native flora, is a distinctive honey originating from southeastern Türkiye. This study evaluated the antiproliferative, anti-tumor, apoptotic, and inflammatory effects of PH on SH-SY5Y human neuroblastoma cells. Cell viability was measured using an MTT assay, while apoptosis was evaluated using an Annexin V-FITC/7-AAD staining test. The RT-qPCR method was used to quantify the expression of IL-1β, IL-6, TNF-α, NF-κB, Caspase-3, MMP-2, MMP-9, BAX, and BCL-2 genes. PH significantly reduced SH-SY5Y cell viability in a dose- and time-dependent manner (p < 0.05-p < 0.01). It induced apoptosis by upregulating BAX and Caspase-3 while downregulating BCL-2 (p < 0.05-p < 0.001). Additionally, it increased NF-κB expression (p < 0.05-p < 0.001) and modulated inflammatory (IL-1β, IL-6, and TNF-α) cytokines (p < 0.05-p < 0.01). MMP-2 and MMP-9 levels were significantly elevated (p < 0.05-p < 0.001), suggesting enhanced extracellular matrix remodeling. These in vitro findings indicate that PH may exert anti-tumor potential and possess immunomodulatory properties. Furthermore, in vitro and in vivo studies are needed to explore its therapeutic applicability.
神经母细胞瘤是一种复杂且异质性的儿科恶性肿瘤。神经母细胞瘤的治疗选择包括手术、化疗、放疗、自体干细胞移植以及新兴的免疫疗法。然而,这些方法常常伴随着氧化应激,凸显了天然抗氧化剂在化学预防和化疗中的潜在作用。蜂蜜长期以来因其药用特性而闻名,包括抗菌、抗炎和抗氧化作用。佩尔瓦里蜂蜜(PH)由在多种本地植物上觅食的蜜蜂生产,是一种源自土耳其东南部的独特蜂蜜。本研究评估了PH对SH-SY5Y人神经母细胞瘤细胞的抗增殖、抗肿瘤、凋亡和炎症作用。使用MTT法测量细胞活力,同时使用膜联蛋白V-FITC/7-AAD染色试验评估凋亡情况。采用RT-qPCR方法定量白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、核因子-κB(NF-κB)、半胱天冬酶-3(Caspase-3)、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)、促凋亡蛋白(BAX)和抗凋亡蛋白(BCL-2)基因的表达。PH以剂量和时间依赖性方式显著降低SH-SY5Y细胞活力(p < 0.05 - p < 0.01)。它通过上调BAX和Caspase-3同时下调BCL-2来诱导凋亡(p < 0.05 - p < 0.001)。此外,它增加了NF-κB的表达(p < 0.05 - p < 0.001)并调节炎症细胞因子(IL-1β、IL-6和TNF-α)(p < 0.05 - p < 0.01)。MMP-2和MMP-9水平显著升高(p < 0.05 - p < 0.001),表明细胞外基质重塑增强。这些体外研究结果表明,PH可能具有抗肿瘤潜力并具有免疫调节特性。此外,需要进行体外和体内研究以探索其治疗适用性。