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    Cynarine Exhibits Antiproliferative Activity and Bcl-2-Mediated Apoptotic Cell Death in Breast Cancer Cells
    (Springer, 2024) Ozdem, Berna; Yildirim, Isil; Cetin, Ayten Kilincli; Tekedereli, Ibrahim
    Cynarine is a biologically active compound that is a derivative of hydroxycinnamic acid and can exhibit a structure-function relationship and therapeutic potential due to its bioactive properties. This study aimed to investigate the antiproliferative and apoptosis activity of the Cynarine compound in breast cancer cells in vitro. MDA-MB-231 MCF7 breast cancer cells and MCF 10A non-cancer cells were used. The MTT method was used to evaluate cell viability. Acolony-forming assay was employed on the cells treated with cynarine to assess their colony-forming capability. Western blotting and annexin-propidium iodide methods with flow cytometry were used to clarify its role in apoptosis. Cell proliferation and colony-forming abilities were reduced in cynarine-treated cells at 56.2%, 67, and 3% in MCF7 and MDA-MB 231, respectively. Apoptotic cell rates after 72 hours of cynarine treatment were found at 7.15%, 42.94%, and 68.67% in MCF 10A, MCF7, and MDA-MB-231 cell lines, respectively. Apoptosis was significantly different in MDA-MB-231 and MCF7 cells treated with cynarine (p < 0.05) It has been concluded that cynarine can be used as a combination therapeutic or a precursor compound to develop new drug combinations to treat breast cancer.
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    GRWD1 Drives Melanoma Growth Through NF-κB Signaling Pathway
    (Mattioli 1885, 2025) Turkmen, Dursun; Ozbey, Rafet; Ozdem, Berna; Alan, Saadet; Cetin, Ayten Kilincli; Baran, Fatma Bengisu; Dogan, Berat
    Introduction: Melanoma is an aggressive skin cancer with high metastatic potential. The oncogenic protein GRWD1 has been implicated in various cancer types, but its role in melanoma remains unclear. Objectives: To examine the effects of GRWD1 knockdown on melanoma cell proliferation, apoptosis, and migration and to evaluate its prognostic significance in melanoma patients. Methods: A combination of in vitro and clinical analyses was performed. A2058 melanoma cells were treated with GRWD1-specific siRNA, and cell proliferation, apoptosis, and migration assays were conducted. Western blotting was used to assess alterations in key oncogenic pathways. Additionally, clinical tissue samples from melanoma patients were analyzed for GRWD1 expression, and Kaplan-Meier survival analysis was performed to determine its prognostic value. Results: GRWD1 was highly expressed in melanoma cells. GRWD1 knockdown significantly reduced cell proliferation (by 63%), impaired colony formation, and induced apoptosis (cleaved caspase-3 levels increased by 17.3%). Migration capacity decreased by 70%, and NF-kappa B pathway activity was suppressed, leading to reduced expression of Bcl-2, Src, and MDM2, while stabilizing p53. TCGA-based analyses revealed that high GRWD1 expression was significantly associated with shorter survival in metastatic melanoma cases (P=0.00029) but showed no correlation with melanoma subtypes. However, in immunohistochemical analysis of clinical samples, no statistically significant correlation was found between GRWD1 staining intensity and survival. Conclusions: GRWD1 plays a crucial role in melanoma progression by enhancing NF-kappa B activity, promoting proliferation, and suppressing apoptosis. While high GRWD1 expression is associated with poor prognosis in public datasets, further clinical validation with larger patient cohorts is needed to confirm its utility as a prognostic biomarker and therapeutic target.