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    Comparative evaluation of cytotoxic and anti-metastatic function of microbial chondroitin sulfate and animal-originated commercial chondroitin sulfate in cancer cells
    (C M B Assoc, 2023) Unver, Tuba; Celik-Uzuner, Selcen; Erenler, Ayse Sebnem
    Cancer has the second-highest mortality rate worldwide after cardiovascular disease. In addition, cervical and breast cancer are two of the leading causes of cancer-related deaths among women. The tumor microenvironment, which consists of cells that form blood vessels, proteins, fibroblasts, and immune cells, is a therapeutic target for cancer therapy. As part of the extracellular matrix (ECM), glycosaminoglycan Chondroitin Sulfate (CS) is related to diverse aspects of tumor growth and metastasis depending on the CS sulfate pattern. This study analyzed the roles of Microbial CS and Commercial CS in tumor growth and metastasis using HeLa cervical cancer cells, MDA-MB-231 metastatic breast cancer cells, and normal fibroblasts. In addition, the role of CS types in wound healing was also assessed comparatively. Microbial CS was more cytotoxic in MDA-MB-231 cells than HeLa compared to Commercial CS. Although both CS reduced cell viability in normal cells, the selective index of Microbial CS in MDA-MB-213 cells was higher than its commercial counterpart. In addition, the role of CS types in wound healing was also assessed comparatively. Both types of CS decreased the cell migration in MDA-MB-231 breast cancer cells, but HeLa cells were more sensitive to Microbial CS than Commercial CS to heal the wound. The wound healing of NIH3T3 cells after Microbial CS was similarly high to the healing after Commercial CS. This preliminary study shows that microbial CS produced by biotechnological methods from a recombinant source created by our team can be an effective therapeutic agent in various types of cancer.
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    Elucidating the antimicrobial and anticarcinogenic potential of methanolic and water extracts of edible Tragopogon coelesyriacus Boiss.
    (Wiley, 2024) Unver, Tuba; Uzuner, Ugur; Celik-Uzuner, Selcen; Gurhan, Ismet; Sivri, Nur Sena; Ozdemir, Zeynep
    Tragopogon coelesyriacus is a pharmacotherapeutic herbaceous plant belonging to the Asteraceae family and consumed as a vegetable. Here, the methanolic and water extracts of T. coelesyriacus were obtained from its aboveground parts (stem, leaves, and flowers), and the phytochemical potentials were investigated by LC-HRMS (liquid chromatography-high resolution mass spectrometry) analysis for the first time. The antibacterial, antifungal, and anticarcinogenic activities of T. coelesyriacus extracts were investigated using experimental and in silico methods. T. coelesyriacus methanol extract revealed remarkable inhibitory activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumonia (MICs = 0.83, 1.67, and 1.67 mg/mL, respectively) compared to Escherichia coli and Enterobacter aerogenes (MIC = 53.3 mg/mL). Inhibitory effects of T. coelesyriacus methanolic extracts were also observed in all Candida species tested, with the highest inhibition on Candida krusei (MIC = 0.83 mg/mL), whereas no inhibitory effect was identified from the water extract. Additionally, both T. coelesyriacus methanolic (IC50 = 86 mu g/mL) and water (IC50 = 92 mu g/mL) extracts revealed significant selective anticarcinogenic effects on AR42J pancreatic cancer cells. HeLa and MDA-MB-231 cells were, however, more resilient to methanol and water extract, respectively. In silico analyses further elucidated the noteworthy antibacterial potential of keracyanin chloride on S. aureus MurB enzyme and the remarkable inhibitory potential of naringin on FYN kinase specific for pancreatic cancer (AR42J) development. In conclusion, T. coelesyriacus phytochemicals with antibacterial, antifungal, and anticancer properties were revealed for the first time, and molecular docking studies on potential targets confirmed good agreement with experimental findings. Therefore, the current studies on T. coelesyriacus provide the basis for investigating new pharmaceutical potentials of other Tragopogon members.