Canan Eroğlu Güneş

Lung cancer is known to have a very high incidence and mortality rate. Trans-cinnamic acid (tCA) is a phenolic compound found in various fruits and vegetables and is known to have many effects such as antimicrobial, anti-inflammatory and anticancer. In this study, molecular docking analysis was performed to predict the binding affinities of tCA toward apoptosis- and ER stress-related target proteins. The effects of tCA on proliferation, apoptosis and endoplasmic reticulum (ER) stress gene expression, colony forming ability, total antioxidant status (TAS) and total oxidant status (TOS) in A549 human lung cancer cells were investigated. Cell proliferation and, expression levels of genes associated with apoptosis and ER stress determined using XTT and qRT-PCR, respectively. ELISA test was used for TAS, TOS and caspase-3 levels. Molecular docking analysis predicted favorable binding affinities of tCA toward the investigated target proteins. The IC₅₀ value of tCA in A549 cells was found to be 2.59 mM at 48 h. Treatment with tCA significantly increased the expression of apoptosis genes including BAX, CASP3, CASP7, CASP8, CASP9, CYCS, and FADD. Among the ER stress-associated genes analyzed, only PERK and CHOP showed significant upregulation following tCA treatment, while no significant changes were observed in the remaining ER stress-related genes. Furthermore, tCA treatment caused a decrease in TAS level but an increase in TOS level. tCA suppressed the ability to form colonies in A549 cells according to the colony assay. In conclusion, tCA inhibited proliferation and colony formation, modulated selected apoptosis- and ER stress-related genes, and altered oxidative stress parameters in A549 cells. These in vitro findings provide preliminary evidence supporting the potential anticancer activity of tCA; however, further protein-level, functional, and in vivo studies are required to confirm the underlying mechanisms and therapeutic potential.

Hepatocellular carcinoma is a progressive tumor with an aggressive nature. Despite many treatment options, survival rates remain low. In this study, the effect of Orox A on hepatocellular carcinoma cells was investigated. Hep3B cells were treated with a range of Orox A, and cell viability was assessed by MTT assays. Subsequent analyses using RT-qPCR demonstrated alterations in the expression of DNA damage and repair genes. To determine the damage in cancer cells, the amount of 8-OHdG and NO in the cells was measured by the ELISA method. Additionally, total antioxidant/oxidant status was measured, and the OSI value was calculated. Flow cytometry analysis was conducted to ascertain the specific cell cycle phase. The IC50 dose of Orox A for hepatocellular carcinoma cells was calculated to be 1385 μM at 24 h. According to the gene expression analysis results, NEIL1, OGG1, ATM and ATR gene expressions increased significantly, while APEX1 gene expression decreased significantly. The amount of 8-OHdG dramatically increased in cancer cells treated with Orox A, whereas the level of NO significantly decreased. Total antioxidant status (TAS) and total oxidant status (TOS) were significantly decreased in Orox A-applied cancer cells, and the oxidative stress index (OSI) was significantly increased. Flow cytometry analysis revealed that Orox A treatment caused G2/M phase arrest in the cell cycle. These findings collectively suggest that Orox A exerts cytotoxic effects on Hep3B cells through mechanisms involving DNA damage, oxidative stress, and cell cycle modulation, making it a promising candidate for further anticancer therapy development.

Background and Objectives: Alzheimer’s disease (AD) has become a serious health problem. Agomelatine (Ago) is a neuroprotective antidepressant. This study aimed to assess how Ago influences behavioral outcomes in AD-like rat model. Materials and Methods: Forty-eight Wistar albino rats were allocated into four groups: Control (C), Alzheimer’s disease-like model (AD), Alzheimer’s disease-like model treated with Ago (ADAgo), and Ago alone (Ago). Physiological saline was injected intrahippocampally in C and Ago animals, whereas Aβ peptide was delivered similarly in AD and ADAgo rats. On day 15, 0.9% NaCl was administered to the C and AD groups, and Agomelatine (1 mg/kg/day) was infused into ADAgo and Ago rats via osmotic pumps for 30 days. Behavioral functions were evaluated using Open Field (OF), Forced Swim (FST), and Morris Water Maze (MWM) tests. Brain tissues were examined histopathologically. Neuritin, Nestin, DCX, NeuN, BDNF, MASH1, MT1, and MT2 transcripts were quantified by real-time PCR. Statistical analyses were performed in R 4.3.1, with p < 0.05 deemed significant. Results: In the FST, swimming, climbing, immobility time, and mobility percentage differed significantly among groups (p < 0.05). In the MWM, AD rats exhibited impaired learning and memory that was ameliorated by Ago treatment (p < 0.05). DCX expression decreased in AD rats but was elevated by Ago (p < 0.05). Nestin levels differed significantly between control and AD animals; MT1 expression varied between control and AD cohorts; and MT2 transcript levels were significantly lower in AD, ADAgo, and Ago groups compared to C (all p < 0.05). Conclusions: Ago exhibits antidepressant-like activity in this experimental AD model and may enhance cognitive function via mechanisms beyond synaptic plasticity and neurogenesis.

Objective: The apoptotic effects of odoroside A on lung cancer cells were studied in our project. We also supported and extended our experimentally-proven results via bioinformatics analysis on human lung cancer tissues. Materials and Methods: In vitro studies were conducted using the A549 cell line. Cell proliferation was evaluated through a CCK-8 assay. For gene expression analysis, the qRT-PCR method was used, while CASP3 protein levels were detected using Western blotting and ELISA. Moreover, the oxidant status of cells was determined by measuring TAS and TOS levels. To construct a protein–protein interaction network, STRING analysis was performed. For the determination of differential expression of apoptosis-related genes, the GEPIA tool was utilized. Kaplan–Meier plots with overall survival, disease-specific survival and progression free intervals were obtained from UCSC Xena to evaluate the prognostic value of caspases. Results: The gene expression levels of CASP3, CASP7, CASP8, CASP9, FAS, and FADD were elevated between 4–16 fold in Odo A-treated lung cancer cells compared to controls. CASP3 protein expression was significantly higher in Odo A-treated cancerous cells than the control group. Low TAS (0.5700 ± 0.0067 in Odo A vs. 0.6437 ± 0.0151 in control) and high TOS (0.82800 ± 0.0208 in Odo A vs. 0.6263 ± 0.0258 in control) levels as well as high OSI values (1.4531 ± 0.0414 in Odo A vs. 0.9748 ± 0.0539 in control) were obtained. Correlogram and protein–protein network analyses suggested strong correlations and interactions among target genes. Lastly, Kaplan–Meier analysis showed no prognostic value of caspases, but potential therapeutic targets in lung cancer. Conclusions: Anti-cancer, prooxidative and therapeutic effects of Odo A on lung cancer cells were shown in our study. These data were supported and extended via computational analyses that we performed. In conclusion, Odo A could be used in clinics to treat patients with lung cancer.

In this study, in order to investigate the anticancer mechanism of Calvatia gigantea extract, edible mushroom species, which belong to Lycoperdaceae family, changes of CCND1, CCND2, CDK4, p21, Akt, Bax, Bcl-2, p53, caspase-3 and caspase-9 were evaluated in A549 lung cancer cells. Cytotoxic effect of C. gigantea extract was evaluated by using XTT (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5 carboxanilide). The C. gigantea extract was treated in a time and dose dependent manner within the range 25 μg/ml–2 mg/ml to determine the IC₅₀ dose. IC₅₀ dose for C. gigantea extract was detected as 500 μg/ml for 72 h. According to expression results, while CCND1, CCND2, CDK4, Akt and Bcl-2 expression clearly decreased, Bax, p53, caspase-3 and caspase-9 expression clearly increased in the dose group cells (A549 cells treated with 500 μg/ml dose of C. gigantea extract for 72 h). However, there was no change in p21 expression. C. gigantea extract induced cell cycle arrest and apoptosis by decreasing the CCND1, CCND2, CDK4, Akt and Bcl-2 expression and by increasing Bax, p53, caspase-3 and caspase-9 expression in A549 cells. Mushrooms are eukaryotic organisms heavily used because of their supposedly anticancer effect. Many mushroom species have been used for medical purposes, as a result of also having many effects such as antibiotic, antiviral and anticancer effects. It is thought that the C. gigantea extract may be a significant agent for treatment of lung cancer as a single agent or in combination with other drugs.