Objective: Lung cancer is the most common cause of morbidity and mortality. Platinum-based chemotherapy, which is the primary line of treatment, offers limited benefit due to drug resistance and side effects. Berberine (BBR), which is characterised by its potent and safe anticancer activity, represents a promising combination option in chemotherapy. To overcome the limitations in lung cancer chemotherapy, we investigated whether BBR and cisplatin (CIS) exert synergistic effects on non-small cell lung cancer cell line (A549) based on cytotoxicity and apoptotic response markers. Methods: The potential cytotoxic effects of the combination treatment were evaluated using the MTT and Chou-Talalay methods. Elisa assays were also performed to measure the levels of the pro-apoptotic protein Bax and the effector protein caspase (Cas)-3. Results: The results showed that BBR alone reduced A549 cell viability in a dose-dependent manner and synergized with CIS (CI =0.34±0.05 at IC50 concentrations). Elisa results showed that the combined treatment (both at IC50 concentrations) modulated apoptotic signalling pathways in A549 cells. Bax and Cas3 protein levels were dramatically enhanced in A549 cells treated with CIS +BBR compared to control (0.5% DMSO) (p < 0.001). Conclusion: Our results suggest that BBR can synergistically enhance the therapeutic effect of CIS in A549 cells. The potential therapeutic efficacy of BBR as part of a combination in current chemotherapy should be supported by in-depth research and clinical studies on the molecular mechanisms associated with cancer.
AMAÇ: Statinlerin bazı hastalarda myopatiye yol açması nedeni ile hastanın tedaviye uyumu azalmakta, ilacın kullanılmasına son verilmekte veya kullanılan ilaç değiştirilmektedir. Bu çalışmada statinlerin myopatiye neden olabileceği iki durum olarak oksidatif stress ve inflamasyon üzerinde çalışılmış ve Kafeik asit fenil ester (CAPE)’in koruyucu rolü deneysel olarak test edilmiştir. GEREÇ VE YÖNTEM: Çalışmada rabdomiyosarkom (RD) hücre hatları kullanılmıştır. Hücreler kontrol, atorvastatin, rosuvastatin, CAPE, atorvastatin+CAPE ve rosuvastatin+CAPE olmak üzere 6 gruba ayrılmıştır. Spektrofotometrik olarak Total Antioksidan Kapasite (TAC), Total Oksidan Kapasite (TOC) ve Oksidatif Stres İndeksi (OSI) analizleri yapılmış; İnterlökin 6 (IL-6) düzeyleri hem protein düzeyinde hem de real time PCR ile mRNA ekpresyonu düzeyinde gösterilmiştir. BULGULAR: Kontrol grubunda 1739 olan OSI atorvastatin uygulaması ile 3814’e çıkmış, atorvastatinin CAPE ile kombinasyonu sonucunda ise 2109’a inmiştir. Rosuvastatin ve Rosuvastatinin CAPE ile kombinasyonu sonucunda kontrol grubuna göre OSI bakımından bir değişiklik olmamıştır. Atorvastin grubunda IL-6 mRNA ekspresyon düzeyleri kontrol grubuna benzer bulunurken, Rosuvastatin grubunda kontrol grubuna nazaran 2,369 kat artış gözlenmiştir. Rosuvastatinin CAPE ile kombinasyonu neticesinde IL-6 mRNA ekspresyon düzeylerinin kontrol grubu seviyesine çekildiği tespit edilmiştir. SONUÇ: Bu çalışmada Atorvastatinin RD hücre hatlarında oksidatif stresi tetiklediği, rosuvastatinin ise IL -6 mRNA ekspresyon düzeyini artırarak proinflamasyona giden sürecin önünü açtığı gözlemlenmiştir. Atorvastatinin neden olduğu oksitadif stresin ve rosuvastatinin neden olduğu inflamasyonun baskılanmasında CAPE kombinasyonunun işlevsel olduğu tespit edilmiştir. Bu bakımdan tedavide atorvastatin ve rosuvastatinin CAPE ile kombinasyonunun statinlerin neden olduğu kas hasarı üzerine hasta yararına olumlu sonuçlarının olabileceği gösterilmiştir.
Purpose This study aims to investigate the role of Resveratrol (RES) and Quercetin (QR) treatments against Benzo(a)pyrene (B(a)p)-induced autophagy in retinal pigment epithelial cells. Methods The IC50 doses of B(a)p,RES and QR in retinal pigment epithelial cells were determined by MTT assay and the relevant agents were administered singly or in combinations to ARPE-19 cells for 24 hours. Occurrence of autophagy in the cells was verified by detection of autophagosomes under fluorescence microscope. Also, the mRNA expression levels of LC3 and Beclin 1 genes were analyzed by RT-PCR to collect further data on autophagy. Caspase-3 and IL-1β levels in lysed cells were analyzed by ELISA. Results Autophagosomes were detected in B(a)p-treated ARPE-19 cell lines, as well as a 1.787-fold increase in LC3 mRNA expression levels. No autophagosome occurred in RES and QR treatments, and a significant decrease in theirpercentage amounts were observed in B(a)p + RES and B(a)p + QR. The mRNA expression levels of LC3 and Beclin 1 also supported these findings.B(a)p had no effect on Caspase-3 levels in ARPE-19 cells, but combined with RES and QR, it increased Caspase-3 levels significantly.IL-1β levels were higher in B(a)p, B(a)p + QR, B(a)p + RES, RES and QR than control group. This rise in IL-1β levels was correlated with suppression of mRNA expression levels of Beclin 1. Conclusion B(a)p exposure caused autophagy in ARPE-19 cells, but did not induce apoptosis. RES and QR treatmentsprevented B(a)p-induced autophagy. Therefore, RES and QR treatments showedprotective effect against potential degenerative diseases caused by chronic exposure to B(a)p.
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