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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.
AtıfScopus2WoS2OpenAlex1
İncele - MakaleAçık Erişim2026Scopus SJRQ2Water extracts of Fucus vesiculosus and Laminaria digitata enhance male reproductive parameters via antioxidant and NO/cGMP mechanisms in rats
Gencoglu, Hasan; Erten, Fusun; Er, Besir; Orhan, Cemal; Acisu, Tutku Can; Sahin, Kazim
Male sexual dysfunction is increasingly prevalent, driving interest in marine algal bioactives as potential natural modulators of reproductive physiology. Brown seaweeds such as Fucus vesiculosus and Laminaria digitata contain phlorotannins, fucoidans, and antioxidant compounds of applied relevance in phycology and biotechnology. This study assessed the effects of standardized water extracts of these two species on reproductive behavior, hormonal status, sperm quality, oxidative balance, and nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signaling in male Sprague–Dawley rats. Animals received the seaweed extracts orally by gavage (300 mg kg⁻1 day⁻1) for 52 days. Both extracts improved male reproductive behavior by reducing the time required to initiate mounting, intromission, and ejaculation (mount latency, intromission latency, and ejaculation latency), while increasing the number of these sexual behaviors during the test period (p < 0.05). Serum follicle-stimulating hormone and testosterone concentrations increased, alongside higher testicular superoxide dismutase, catalase, and glutathione peroxidase activities and lower malondialdehyde levels. Sperm count and motility improved, particularly with L. digitata extract. Western blot analyses revealed phosphorylated phosphodiesterase-5, endothelial NO synthase, and cGMP levels, with reduced endothelin-1 in testicular and epididymal tissues (p < 0.05–0.001). These findings indicate that extracts of F. vesiculosus and L. digitata, chosen for their well-documented antioxidant and phlorotannin-rich profiles, confer protective and prosexual effects associated with enhanced antioxidant defense and upregulation of NO/cGMP-related pathways, with the L. digitata extract exhibiting comparatively stronger activity.
- MakaleAçık Erişim2024Scopus SJRQ1Impact of a Novel Valerian Extract on Sleep Quality, Relaxation, and GABA/Serotonin Receptor Activity in a Murine Model
Sahin, Kazim; Gencoglu, Hasan; Korkusuz, Ahmet Kayhan; Orhan, Cemal; Aldatmaz, İsmail Ertuğ; Erten, Fusun; Er, Besir; Morde, Abhijeet; Padigaru, Muralidhara; Kilic, Ertugrul
Insomnia is a major global health issue, highlighting the need for treatments that are both effective and safe. Valerian extract, a traditional remedy for sleep problems, offers potential therapeutic options. This research examined the potential sleep-enhancing effects of VA (Valerian Pdr%2) in mice. The study evaluated sleep quality by comparing the impact of the VA extract against melatonin on brain activity, using electrocorticography (ECoG) to assess changes in brain waves. For this purpose, the study utilized two experimental models on BALB/c mice to explore the effects of caffeine-induced insomnia and pentobarbital-induced sleep. In the first model, 25 mice were assigned to five groups to test the effects of caffeine (caffeine, 7.5 mg/kg i.p) alone, caffeine with melatonin (2 mg/kg), or caffeine with different doses of valerian extract (100 or 300 mg/kg) given orally on brain activity, assessed via electrocorticography (ECoG) and further analyses on the receptor proteins and neurotransmitters. In the second model, a different set of 25 mice were divided into five groups to examine the impact of pentobarbital (42 mg/kg) alone, with melatonin, or with the valerian extract on sleep induction, observing the effects 45 min after administration. The study found that ECoG frequencies were lower in groups treated with melatonin and two doses of valerian extract (100 and 300 mg/kg), with 300 mg/kg showing the most significant effect in reducing frequencies compared to the caffeine control group, indicating enhanced sleep quality (p < 0.05). This was supported by increased levels of serotonin, melatonin, and dopamine and higher levels of certain brain receptors in the melatonin and valerian extract groups (p < 0.05). Modulatory efficacy for the apoptotic markers in the brain was also noted (p < 0.05). Additionally, melatonin and both doses of VA increased sleep duration and reduced sleep onset time compared to the pentobarbital control, which was particularly notable with high doses. In conclusion, the findings suggest that high doses (300 mg/kg) of valerian extract enhance both the quantity and quality of sleep through the GABAergic pathway and effectively increase sleep duration while reducing the time to fall asleep in a pentobarbital-induced sleep model in mice.
AtıfScopus19OpenAlex19İncele - MakaleYalnız künye2020Effects of Taurine on the Levels of PPARγ, IRS-1, HSP-27, HSP-72 and Histopathological Changes in Kidney of the Diabetic Rats
Tuzcu, Mehmet; Erten, Fusun; Gencoglu, Hasan
The objective of this study was to investigate the effects of taurine on PPAR-γ, IRS-1, HSP-27, and HSP-72 levels along with the kidney histopathological changes in streptozotocin (STZ) induced diabetic rats. In the study, 40 Wistar albino male rats were divided into four groups. (i) Control group, (ii) Taurine, rats received taurine with drinking water (2%); (iii) STZ, rats were injected with STZ (60 mg/kg i.p. as single dose) and (iv) STZ+Taurine, rats received taurine and injected with STZ. After 8 weeks of the study, the Taurine group was found to be statistically indifferent to the control group in terms of PPAR-γ, IRS-1, HSP-27, and HSP-72 levels (P>0.05). However, PPAR-γ (P<0.01), IRS-1 and HSP-72 (P<0.001) levels decreased in the STZ group. HSP-27 (P<0.01) levels increased in the STZ group as compared with the control. On the other hand, there were histopathological changes in the STZ group. The intensity of histopathological changes induced by STZ was decreased in the STZ+Taurine group. As a result, the taurine supplementation may prevent and treat the kidney damage in diabetic rats
- MakaleAçık Erişim2020Deneysel Otizm Spektrum Bozukluğu Modeli Oluşturulan Sıçanlarda Likopenin Beyin IL–6, IL–10, FGF–2 ve NGF Düzeyleri Üzerine Etkisi
Sahin, Kazim; Erten, Fusun; Gencoglu, Hasan
Otizm spektrum bozukluğu (OSB), batılı ve gelişmiş toplumlarda artan bir sorundur. Doğası gereği büyük ölçüde genetik olmasına rağmen,birçok çevresel faktör hassas popülasyonlarda OSB'yi tetiklemede rol oynayabilmektedir. Propiyonik asit (PPA) uygulaması, anormal nöralhücre organizasyonunu ve ardından otizm benzeri nörodavranışları içeren kritik değişiklikleri indükleyebilmektedir. Likopen vemetabolitleri beyinde kontrol edilebildiğinden, likopenin merkezi sinir sisteminde nöroprotektif etkileri olabileceği ve başlıca beyin biyobelirteçleri üzerinde modülasyona neden olabileceği düşünülmektedir. Bu çalışmada, 35 adet üç haftalık yaşta Sprague Dawley ırkı erkeksıçan 5 gruba ayrıldı: i) Kontrol. ii) PPA; (500 mg/kg/ip). iii) PPA+LI (PPA’ya ek olarak, 5 mg/kg/gün intragastrik likopen verilen grup), iv)PPA+LII; (PPA’ya ek olarak, 10 mg/kg/gün intragastrik likopen verilen grup), v) PPA+LIII, (PPA’ya ek olarak, 20 mg/kg/gün intragastriklikopen verilen grup). Çalışma sonunda hayvanlar dekapite edildi ve beyin dokuları alınarak homojenize edildi ve SDS-PAGE ve westernblot teknikleriyle beyinde enflamatuar sitokinler interlökin 6 ve 10 (IL6/IL10) ile temel fibroblast büyüme faktörü (FGF-2) ve sinir büyümefaktörü (NGF) düzeylerinin değişimi tespit edildi. Elde edilen sonuçlara göre 35 günlük uygulama sonunda likopenin, PPA ile OSB modelioluşturulan sıçanlarda, PPA’ya bağlı olarak artan IL–6 ve IL-10 düzeylerini özellikle PPA+LIII ve PPA+LII grubunda düşürdüğü tespit edildi.Bununla birlikte, FGF–2 ve NGF düzeyleri de her üç likopen grubunda da belirgin olarak PPA verilen gruba göre artış gösterdi (P<0,0001).Sonuç olarak, likopen, PPA ile indüklenen OSB benzeri nöropatolojik bozuklukları beyin inflamatuar sitokinleri ve büyüme faktörleriniregüle ederek azaltabilir.
