Browsing by Author "Alvur, Ozge"

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The Dicyano Compound Induces Autophagic or Apoptotic Cell Death Via Twist/C-myc Axis Depending on Metastatic Characteristics of Breast Cancer Cells
(Springer, 2022) Alvur, Ozge; Kucuksayan, Hakan; Baygu, Yasemin; Kabay, Nilgun; Gok, Yasar; Akca, Hakan
Background Breast cancer (BC) is a heterogeneous disease with various subtypes, therefore, the illumination of distinctive mechanisms between subtypes for the development of novel treatment strategies is important. Here, we revealed the antiproliferative effects of our customized dicyano compound (DC) on BC cells. Methods and results We determined the antiproliferative effect of the DC on non-metastatic MCF-7 and metastatic MDA-MB-231 cell lines by MTT. We evaluated protein levels of LC3BI-II and p62 to detect effects of the DC on autophagy. Furthermore, we examined whether the DC induce apoptosis in MCF-7 and MDA-MB-231 cells by performing TUNEL and western blotting. We showed that the DC induces autophagic cell death in MDA-MB-231 while it leads to apoptosis in MCF-7, demonstrating that DC can induce different cell death mechanisms in BC cells according to what they represent subtypes. To understand the reason of different cell response to the DC, we evaluated the expressions of several regulator proteins involved in survival, cell arrest and proliferation. All findings revealed that c-Myc expression is directly correlated with autophagy induction in BC cells and it could be a marker for the selection of cell death mechanism against anti-cancer drugs. Interestingly, we showed that the overexpression of Twist, responsible for metastatic features of BC cells, imitates the effects of autophagy on c-Myc expression in MCF-7 cells, indicating that it is implicated in both the regulation of c-Myc as a upstream factor and subsequently the selection of cell death mechanisms. Conclusion Taken together, we suggest that Twist/c-Myc axis may have a role in different response to the DC-induced cell death pathways in BC subtypes with different invasive characteristics.
The Effects of Oral Supplementation of Carvacrol on Autophagy and Epithelial To Mesenchymal Transition Regulation in Uv-Induced Skin Damage
(Taylor & Francis Ltd, 2025) Alvur, Ozge; Ozkol, Halil; Altindag, Fikret; Ozkol, Hatice Uce; Evyapan, Gulsah; Akar, Sakine
ObjectiveThe skin is the biggest organ of the body being most exposed to UV radiation (UVR). Many skin diseases may develop due to UV exposure. Thus, it is extremely important to reveal molecules that can prevent these diseases.Material and methodCarvacrol (CVC), a liquid phenolic monoterpenoid is found in thyme and some plants related to thyme. In our study, for the first time in the literature we aimed to determine the effects of CVC on autophagy and Epithelial to Mesenchymal Transition (EMT) mechanisms in skin damage of rats exposed to combined UVA and UVB radiation. For this purpose, twenty-eight rats were divided into four groups: I (Control), II (CVC alone), III (UVA + UVB), IV (UVA + UVB + CVC). While UVA + UVB was applied without any treatment in Group III, this application was performed with CVC support in Group IV. As for the animals in Group II, only carvacrol was given. On the 30th day of the trial, expression of certain genes playing a role in autophagy and EMT pathways were evaluated at mRNA and protein level by qRT-PCR and immunohistochemical staining in the shaved back skin tissues of rats.ResultsBased on our results, it can be concluded that CVC may prevent autophagic cell death by suppressing autophagy and it might support the wound healing process by inducing EMT in UV-induced skin damage. The molecular mechanisms of the effect of CVC on autophagy and EMT mechanisms should be clarified in further studies.
The Preventive Effects of Natural Plant Compound Carvacrol Against Combined Uva and Uvb-Induced Endoplasmic Reticulum Stress in Skin Damage of Rats
(Springernature, 2024) Evyapan, Gulsah; Ozkol, Halil; Ozkol, Hatice Uce; Alvur, Ozge; Akar, Sakine
The skin is constantly exposed to a variety of environmental stressors, including ultraviolet (UV) radiation. Exposure of the skin to UV radiation causes a number of detrimental biological damages such as endoplasmic reticulum (ER) stress. The ER stress response is a cytoprotective mechanism that maintains homeostasis of the ER by increasing the capacity of the ER against the accumulation of unfolded proteins in the ER. Carvacrol (CRV) is a monoterpenoid phenol found in essential oils with antimicrobial and anti-inflammatory activities. We investigated for the first time in the literature the potential protective role of CRV against combined UVA and UVB-induced skin damage by targeting the ER stress pathway in a rat model. For this purpose, expressions of Grp78, Perk, Atf6, Ire-1, Chop, Xbp1, Casp12, elF2 alpha, and Traf2 genes related to ER stress were analyzed by RT-PCR and protein expression levels of GRP78, ATF6, CHOP, and XBP1 were determined by ELISA assay in tissue sections taken from the back of the rats. As a result of analysis, it was seen that the expression levels of aforementioned ER stress genes increased significantly in the UVA + UVB irradiated group compared to the control group, while their expression levels decreased markedly by supplementation of CRV in UVA + UVB + CRV group. With regard to expressions of foregoing proteins, their levels escalated notably with UVA + UVB application and decreased markedly by CRV supplementation. In conclusion, present study revealed that CRV ameliorates UVA + UVB-induced ER stress via reducing the expression of mRNA as well as proteins involved in the unfolded protein response (UPR) pathway and inducing apoptosis as evidenced from high Caspase12 level.
The Triazole Linked Galactose Substituted Dicyano Compound Can Induce Autophagy in Nsclc Cell Lines
(Elsevier, 2019) Alvur, Ozge; Tokgun, Onur; Baygu, Yasemin; Kabay, Nilgun; Gok, Yasar; Akca, Hakan
As seen in other types of cancer, development of drug resistance in NSCLC treatment causes adverse effects on disease fighting process. Recent studies have shown that one of the drug resistance development mechanisms is that cancer cells may acquire the ability to escape from cell death. Therefore, development of anticancer drugs which have the strategy to redirect cancer cells to any cell death pathways may provide positive results for cancer treatments. Autophagy may be a target mechanism of alternative cancer treatment strategy in cases of blocked apoptosis. There is also a complex molecular link between autophagy and apoptosis, has not been fully understood yet. The dicyano compound which we used in our study caused cell death in NSCLC cell lines. When we analyzed the cells which were treated with dicyano compound by transmission electron microscope, we observed autophagosome structures. Upon this result, we investigated expression levels of autophagic proteins in the dicyano compound-treated cells by immunoblotting and observed that expression levels of autophagic proteins were increased significantly. The TUNEL assay and qRT-PCR for pro-apoptotic and anti-apoptotic gene expression, which we performed to assess apoptosis in the dicyano compound-treated cells, showed that the cell death does not occur through apoptotic pathway. We showed that the dicyano compound, which was developed in our laboratories, may play a role in molecular link between apoptosis and autophagy and may shed light on development of new anticancer treatment strategies.