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    Antiproliferative and apoptotic effects of Pervari honey on SH-SY5Y neuroblastoma cells
    (Humana Press Inc, 2025) Altin-Celik, Pinar; Derya-Andeden, Muazzez; Eciroglu-Sarban, Hamiyet; Donmez-Altuntas, Hamiyet
    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 T & uuml;rkiye. 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-1 beta, IL-6, TNF-alpha, NF-kappa B, 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-kappa B expression (p < 0.05-p < 0.001) and modulated inflammatory (IL-1 beta, IL-6, and TNF-alpha) 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.
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    Iturin A and Gramicidin A inhibit proliferation, trigger apoptosis, and regulate inflammation in breast cancer cells
    (Elsevier, 2024) Altin-Celik, Pinar; Eken, Ahmet; Derya-Andeden, Muazzez; Eciroglu, Hamiyet; Uzen, Ramazan; Donmez-Altuntas, Hamiyet
    Biosurfactants with antibiotic, antiviral, anti-tumor, and immunomodulatory properties appear to have potential in cancer treatment due to their lack of known toxicities compared with conventional chemotherapy. However, there are few studies on the use of biosurfactants for the treatment of breast cancer. In this study, to develop a new strategy for breast cancer treatment, we evaluated the anti-proliferative, anti-inflammatory, anti-tumor, and apoptotic effects of two different biosurfactants (Iturin A and Gramicidin A) from bacillus in both single and binary combination on two breast cancer cell lines (MDA-MB-231 and MCF-7, which is estrogen receptornegative and positive, respectively). First, the anti-proliferative effects of Iturin A and Gramicidin A, both single and in combination, were explored by MTT assay. Then, the effects of Iturin A and Gramicidin A on inflammatory factors were evaluated using the ELISA method. Apoptosis was assessed using Annexin V-PE/7-AAD and Giemsa staining methods. RT-qPCR analysis was used to evaluate the expressions of several cytokines with anti-tumor and apoptotic properties and the apoptotic BAX and BCL2 genes. Biosurfactants showed antiproliferative and anti-tumor properties by decreasing the viability of MDA-MB-231 and MCF-7 cells depending on concentration and time (p < 0.05-p<0.01). Biosurfactants induced apoptosis by stimulating apoptotic cell death (p < 0.05-p<0.001) and by increasing BAX and decreasing BCL2 gene expression levels (p < 0.05p<0.001) in breast cancer cells. Biosurfactants also regulated the expressions of extracellular and intracellular cytokines (IL-2, IL-6, IL-12, IL12RB2, TGF beta, TNF alpha, VEGF) and chemokines (IL-8, CCL2, CXCL10) in breast cancer cells (p < 0.05-p<0.01). Both single and binary combination applications of Iturin A and Gramicidin A biosurfactants, may potentially treat breast cancer patients, and the in vitro results presented here warrant further in vivo studies.