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- MakaleAçık Erişim2026Scopus SJRQ2Synergistic Effects of Caffeine and Paclitaxel in Breast Cancer Cells: Mechanistic Insights Into NF-κB and Nrf2 Signaling
Gencoglu, Hasan; Delioglu, Saime; Nergiz, Mehmet Akif; Metin, Rumeysa; Erten, Fusun; Tokmak, Muhammed; Orhan, Cemal; Sahin, Kazim
Breast cancer remains one of the most prevalent malignancies among women. Recent studies have explored the potential of phytochemicals such as caffeine as chemosensitizing agents in enhancing the efficacy of standard chemotherapeutics like paclitaxel. This study aimed to investigate the cytotoxic, apoptotic, inflammatory, and oxidative stress-related effects of caffeine alone and in combination with paclitaxel in MCF-7 cells. Cells were treated with various concentrations of caffeine (1–100 mM), paclitaxel (0–350 µg/mL), and their combinations for 24, 48, and 72 h. Cell viability was assessed using the MTS assay, and IC₅₀ values were calculated. The expression levels of Bax, Bcl-2, NF-κB, and Nrf2 proteins were analyzed by Western blotting. Both caffeine and paclitaxel induced time- and dose-dependent reductions in MCF-7 cell viability. The combination treatment showed synergistic cytotoxicity, with significantly lower IC₅₀ values compared to single-agent treatments. Western blot analysis showed that both treatments boosted pro-apoptotic Bax and decreased anti-apoptotic Bcl-2, with slightly less effect in the combination group. NF-κB levels increased considerably in caffeine and paclitaxel groups, but were lower in the combination group compared to paclitaxel alone, suggesting a possible reduction in inflammatory signaling. Nrf2 expression increased significantly with caffeine, suggesting oxidative stress responses. In MCF-7 cells, caffeine enhanced paclitaxel's pro-apoptotic and cytotoxic actions and modified inflammation and oxidative stress pathways in a complicated, dose-dependent manner. Cytotoxicity was synergistic; however, apoptotic and stress indicators may be antagonistic. In clinical circumstances, caffeine may be an adjuvant in breast cancer treatment, however mechanistic and in vivo investigations are needed.
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İncele - MakaleAçık Erişim2025Scopus SJRQ1Effects of Integrated Extracts of Trigonella foenum-graecum and Asparagus racemosus on Hot Flash-like Symptoms in Ovariectomized Rats
Erten, Fusun; Er, Besir; Ozmen, Ramazan; Tokmak, Muhammed; Gokdere, Ebru; Orhan, Cemal; Morde, Abhijeet A.; Padigaru, Muralidhara; Sahin, Kazim
Vasomotor symptoms, such as hot flashes (HFs), commonly affect women during menopause, leading to a reduced quality of life. The current study evaluates the combined effect of active components Asparagus racemosus (AR) and Trigonella foenum-graecum (TFG) in a single oral formulation (IAT) for alleviating menopausal symptoms in ovariectomized rats. Following bilateral ovariectomy, the animals were randomly assigned to nine groups: (1) Control, (2) Ovariectomy (OVX), (3) OVX+TA1 (TA: Combination of Trigonella and Asparagus; TFG 30 mg/kg + AR 30 mg/kg), (4) OVX+TA2 (TFG 30 mg/kg + AR 15 mg/kg), (5) OVX+TA3 (TFG 15 mg/kg + AR 30 mg/kg), (6) OVX+TA4 (TFG 40 mg/kg + AR 30 mg/kg), (7) OVX+TA5 (TFG 30 mg/kg + AR 40 mg/kg), (8) OVX+IAT1 (IAT: Integrated Asparagus and Trigonella; TFG+AR integrated extract, 30 mg/kg), and (9) OVX+IAT2 (TFG+AR integrated extract, 60 mg/kg). On the 8th day of treatment, tail and skin temperatures were recorded every 30 min for 24 h. Ovariectomized rats exhibited menopausal symptoms, such as hormonal imbalances and elevated skin temperature. Administration of AR, TFG, and IAT significantly decreased serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and cortisol while increasing estradiol, progesterone, and dopamine (p < 0.0001), effectively alleviating hot flash-like symptoms. Additionally, they mitigated ovariectomy-induced oxidative stress by lowering malondialdehyde (MDA) levels and restoring antioxidant enzyme activity. Ovariectomized rats exhibited increased expression of a proto-oncogene (c-FOS), gonadotropin-releasing hormone (GnRH), Kisspeptin, Neurokinin B (NKB), and Transient receptor potential vanilloid 1 (TRPV1), along with reduced expressing brain-derived neurotrophic factor (BDNF) levels, which were reversed by treatment, especially with the IAT2 combination. The AR and TFG combination, particularly in IAT formulations, showed strong potential in alleviating menopausal symptoms in ovariectomized rats. These findings suggest that the combination of AR and TFG extracts could be a natural alternative for managing postmenopausal symptoms by restoring reproductive hormone levels, regulating lipid profiles, and enhancing antioxidant defense systems.
AtıfScopus8WoS8OpenAlex6İncele - MakaleAçık Erişim2024Scopus SJRQ1Novel formulations ameliorate osteoarthritis in rats by inhibiting inflammation and oxidative stress
Erten, Fusun; Ozdemir, Oguzhan; Tokmak, Muhammed; Durmus, Ali Said; Ozercan, Ibrahim Hanifi; Morde, Abhijeet; Padigaru, Muralidhara; Sahin, Kazim
The study tested new oral plant-based formulations (F) on rats with monosodium iodoacetate (MIA)-induced osteoarthritis, measuring inflammation, antioxidant levels, paw size, stride, and analyzing knee joint images. Fifty-six female Sprague Dawley rats were allocated into 8 groups: (1) Control, (2) MIA (OA induced with MIA), (3) MIA + F1 [curcuminoids+gingerols+acetyl-11-keto-β boswellic acid (AKBA)], (4) MIA + F2 (curcuminoids+Withania glycosides+AKBA), (5) MIA + F3 (curcuminoids+total withanolides+AKBA), (6) MIA + F4 (curcuminoids, AKBA), (7) MIA + UCII (type II collagen), and (8) MIA + GCHON (Glucosamine Chondroitin). Treatments F1 to F4 reduced right joint diameter and improved stride length and paw area in OA rats. Despite improvements with treatments F1 to F4, there was no significant difference between these groups (p >.05). In OA animals, F1 to F4 treatments decreased MDA levels and increased antioxidant enzymes activities (p <.001). This was done by reducing levels of inflammatory markers and enzymes like IL-1β, IL-6, MMP-8, TNF-α, CRP, COMP, and LOX-5, while increasing the anti-inflammatory cytokine IL-10. In conclusion, these plant-based treatments significantly reduced osteoarthritis severity, slowed disease progression by reducing inflammation, and protected joints from damage, showing a protective effect in rats with induced osteoarthritis, likely due to their anti-inflammatory and antioxidant properties.
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