Meme kanseri hücrelerinde enerji regülasyonunun hücre sağ kalımı üzerine etkileri
Küçük Resim Yok
Tarih
2025
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
İnönü Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: Kanser hücreleri, artmış nikotinamid fosforibosiltransferaz (NAMPT) ekspirasyonu nedeniyle sürekli nikotinamid adenin dinükleotit (NAD) sentezleyerek oksitlenmiş NAD fosfat (NADP+) havuzunu arttırır. Böylece pentoz fosfat yolu (PFY) aracılığıyla indirgenmiş NADP (NADPH) üretimi sürdürülür. Meme kanseri hücreleri, indüklenen PFY ile büyümektedir. Bu nedenle, NAD metabolizmasını hedef alarak, enerji regülasyonu ile hücresel sağkalımı sürecinin araştırılması hedeflendi. Materyal ve Metot: MCF7 ve MDAMB231 hücreleri büyütüldükten sonra dörder gruba ayrıldı. MCF7-CG'ye ve MDAMB231-CG'ye hiçbir madde uygulanmadı. MCF7-FG'ye 10 mM FK866, MCF7-QG'ye 40 mM kuersetin, MCF7-AG'ye 10 mM apigenin verildi. MDAMB231-FG'ye 10 mM FK866, MDAMB231-QG'ye 40 mM kuersetin, MDAMB231-AG'ye 10 mM apigenin uygulandı. Ertesi gün hücreler büyüme ortamlarından ayrılarak NAD/NADH oranı, reaktif oksijen türleri (ROS), glutatyon-s-transferaz (GST) aktiviteleri, interlökin (IL)-1? ve tümör nekroz faktör (TNF)-?, geçici reseptör potansiyel (TRP) kanal (TRPC) 1 ve TRPC 4 protein düzeyleri ile endoplazmik retikulum (ER) stres belirteçleri ölçüldü. Elde edilen bulgular uygun istatiksel yöntemleriyle değerlendirildi. Bulgular: Her iki hücre hattında apigenin ve kuersetin NAD miktarlarında artışa yol açarken FK866 verilen hücrelerde düşüş gözlendi. Bununla beraber apigenin kuersetine kıyasla daha iyi bir NAD koruyucu olduğu halde kuersetinin antioksidan savunma mekanizmasına daha güçlü etki ettiği gözlendi. Hem MCF7 hem de MDAMB231 hücrelerinde, gruplar arasında IL-1?, TNF ?, TRPC 1, TRPC4, GRP78, ATF4, CHOP ve kaspaz 3 düzeylerinde istatistiksel olarak önemli farklılıklar bulundu (p<0.05). Sonuç: Hücresel enerji metabolizmasında önemli bir rol üstlenen NAD molekülünün hedef alınması ile meme kanseri hücrelerinde kalsiyum depoları tüketilerek oksidatif hasar ve ER stresi meydana gelebilir. Bunun sonucunda hücrelerin malign aktiviteleri önlenebilir. Ayrıca tümör hücrelerinin doğrudan kalsiyum kanallarına yönelik geliştirilebilecek ilaçlar ile tümöral aktivite yönetilebilir.
Aim: The cancer increases the oxidized NAD phosphate (NADP+) pool by continuously synthesizing nicotinamide adenine dinucleotide (NAD) due to the growth of nicotinamide phosphoribosyltransferase (NAMPT). Reductive NADP (NADPH) is produced via the pentose phosphate pathway (PFY), which is induced in breast cancer. Targeting NAD metabolism may help manage energy regulation for survival. Material and Method: MCF7 and MDAMB231 cells were split into four groups after growth. MCF7-CG and MDAMB231-CG received no treatment. MCF7-FG and MDAMB231-FG were treated with 10 mM FK866, MCF7-QG, and MDAMB231-QG with 40 mM quercetin, and MCF7-AG and MDAMB231-AG with 10 mM apigenin. The following day, cells were separated from their growth medium. Measurements were taken for NAD/NADH ratio, reactive oxygen species (ROS), glutathione-s-transferase (GST) activities, interleukin (IL)-1?, tumor necrosis factor (TNF)-?, TRPC 1 and TRPC 4 protein levels, and ER stress markers. The findings were analyzed using appropriate statistical methods. Results: Apigenin and quercetin increased NAD levels in both cell lines, but a decrease was noted in cells given FK866. Apigenin was more effective in protecting NAD, while quercetin enhanced antioxidant defense. Significant differences in IL-1?, TNF ?, TRPC 1, TRPC4, GRP78, ATF4, CHOP, and caspase three levels were found between groups in both MCF7 and MDAMB231 cells (p<0.05). Conclusion: Targeting the NAD molecule, crucial for cellular energy metabolism, can deplete calcium stores in breast cancer, leading to oxidative damage and ER stress and potentially preventing malignancy. According to our findings, tumoral activity can be managed with drugs that can be developed directly targeting the calcium channels of tumor cells.
Aim: The cancer increases the oxidized NAD phosphate (NADP+) pool by continuously synthesizing nicotinamide adenine dinucleotide (NAD) due to the growth of nicotinamide phosphoribosyltransferase (NAMPT). Reductive NADP (NADPH) is produced via the pentose phosphate pathway (PFY), which is induced in breast cancer. Targeting NAD metabolism may help manage energy regulation for survival. Material and Method: MCF7 and MDAMB231 cells were split into four groups after growth. MCF7-CG and MDAMB231-CG received no treatment. MCF7-FG and MDAMB231-FG were treated with 10 mM FK866, MCF7-QG, and MDAMB231-QG with 40 mM quercetin, and MCF7-AG and MDAMB231-AG with 10 mM apigenin. The following day, cells were separated from their growth medium. Measurements were taken for NAD/NADH ratio, reactive oxygen species (ROS), glutathione-s-transferase (GST) activities, interleukin (IL)-1?, tumor necrosis factor (TNF)-?, TRPC 1 and TRPC 4 protein levels, and ER stress markers. The findings were analyzed using appropriate statistical methods. Results: Apigenin and quercetin increased NAD levels in both cell lines, but a decrease was noted in cells given FK866. Apigenin was more effective in protecting NAD, while quercetin enhanced antioxidant defense. Significant differences in IL-1?, TNF ?, TRPC 1, TRPC4, GRP78, ATF4, CHOP, and caspase three levels were found between groups in both MCF7 and MDAMB231 cells (p<0.05). Conclusion: Targeting the NAD molecule, crucial for cellular energy metabolism, can deplete calcium stores in breast cancer, leading to oxidative damage and ER stress and potentially preventing malignancy. According to our findings, tumoral activity can be managed with drugs that can be developed directly targeting the calcium channels of tumor cells.
Açıklama
Anahtar Kelimeler
Fizyoloji, Physiology
