Browsing by Author "Evyapan, Gulsah"

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Combination Treatment With Ornidazole and Dacarbazine Inhibits Proliferation, Cell Migration and Induces Dna Damage in Melanoma Cells
(Natl inst Science Communication-niscair, 2024) Evyapan, Gulsah; Luleyap, H. Umit; Comertpay, Gamze; Aksoy, Gulsevinc; Kaplan, H. Mahir; Oksuz, Hale; Pazarci, Percin
Metastatic cancers are responsible for 90% of cancer related deaths and melanoma is known as one of the deadliest cancers. Dacarbazine (DTIC) for metastatic melanoma has become an approved first-line treatment in routine clinical practice. However, response rates to single-drug therapy with dacarbazine are quite low. Therefore, combination drug therapy as a method of treatment that combines two or more therapeutic agents is the cornerstone of cancer therapy. Here, we examined the effects of the combination of ornidazole, a derivative of 5-nitroimidazole which is active against protozoa and anaerobic bacteria, and DTIC on melanoma cells to investigate novel advanced combination therapies for melanoma. Doses in this study are 0, 800 and 1200 mu g/mL for ornidazole, 0, 5, 25, 50, 100, 200, 300, 600, 1200 mu M/L for DTIC and 800 mu g/mL+100 mu M/L, 800 mu g/mL+200 mu M/L, 1200 mu g/mL+100 mu M/L, 1200 mu g/mL+200 mu M/L for ornidazole+DTIC combination. Treatment effect of ornidazole and DTIC as a single-agents and in combination on cell viability was investigated with crystal violet and MTT assays. As well as the effect of them on migration ability was assessed by wound healing assay, the effect of them on DNA damage induction was evaluated by comet assay in B16F10 melanoma cells in vitro. Our data showed that combination treatment with ornidazole and DTIC markedly inhibited cancer cell proliferation and migration. DNA damage was also significantly induced by this combination treatment. Our study showed that ornidazole/DTIC combination drug therapy has more effective therapeutic potential for melanoma compared to DTIC therapy alone. In conclusion, our findings suggest that combination therapy with ornidazole/ DTIC could serve as a new and valuable approach for melanoma treatment.
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.
Mirnas in Melanoma: Diagnostic, Prognostic, and Therapeutic Strategies
(Biomedpress, 2024) Evyapan, Gulsah; Ozdem, Berna; Aksoy, Gulsevinc
Melanoma is a highly aggressive and deadly form of skin cancer, with its incidence and mortality rates increasing significantly worldwide. Recent research suggests that miRNA-based therapies could help improve outcomes for melanoma patients by controlling gene expression at the post transcriptional level, which affects how the tumor grows and spreads. This review aims to examine the role of microRNAs (miRNAs) in melanoma progression, highlighting their potential as therapeutic targets and exploring how they may be utilized in diagnostic and prognostic processes.
Ornidazole Inhibits the Angiogenesis and Migration Abilities of Non-Small Cell Lung
(Humana Press inc, 2024) Evyapan, Gulsah; Senturk, Nesrin Cetinel; Celik, Ibrahim Seyfettin
Background: Around the world, non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths among all cancers. Despite advancements in new therapeutic approaches over the past few decades, the five-year survival rate still remains disappointing. The lack of effective anti-angiogenic and anti-migration drugs is the biggest obstacle to the treatment of metastatic lung cancer. Therefore, there is a need to develop new and effective therapeutic compounds targeting anti-angiogenic and anti-migration pathways for the treatment of lung cancer. Ornidazole is a nitroimidazole agent widely used in the treatment of parasitic infections such as trichomonas vaginalis, amebiasis and giardiasis. This study aimed to investigate the anti-proliferative, anti-angiogenic and anti-mitotic activities of the anti-parasitic drug Ornidazole in two human lung cancer cell lines (A549, H1299). Methods: We determined the effects of Ornidazole, on cell viability, apoptosis, migration, angiogenesis and metastatic ability against NSCLC in lung cancer cell lines. Its action on the mRNA and protein expression levels of VEGFA, VEGFR2, NRP1, Casp9, Casp3, Bax, Bcl-2, PIK3CA, AKT, MTOR, PTEN and FOX3A was assessed. Furthermore, in this study the effects on cell migration, cell viability and proliferation was evaluated through wound healing, MTT and Crystal violet assays. Results: This study demonstrated that Ornidazole effectively reduces cell viability and migration ability, inhibits angiogenesis and metastatic abilities in NSCLC cells. Conclusions: In conclusion, these results may shed light on the treatment of NSCLC, and we suggest the anti-parasitic drug Ornidazole as a new agent with potential anti-angiogenic and anti-mitotic activity by interfering with the molecular pathways that trigger tumor angiogenesis and migration.
Ornidazole Inhibits the Angiogenesis and Migration Abilities of Non-Small Cell Lung Cancer (Nsclc) Via Downregulation of Vegfa/Vegfr2 and Pi3k/Akt Pathways (Sept, 10.1007/S12013-024-01358-x, 2024)
(Humana Press inc, 2025) Evyapan, Gulsah; Senturk, Nesrin Cetinel; Celik, Ibrahim Seyfettin
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.