Boron Increases the Viability of Human Cancer and Murine Fibroblast Cells After Long Time of Cryopreservation

DergiPark: 758920trkjnatThrough the process of cryopreservation, cells are stored at very low temperature for a long time to decrease the biological and chemical reactions in viable cells. In this process, the administration of cryoprotective agents is crucial since cryopreservation is regarded as a leading process in various research fields such as biotechnology, clinical medicine and maintenance of both animal and plant cells. Even after a long time of storage in very low temperatures, a recovery is achieved by cryo-preservative agents that act on cellular metabolism and biophysiology of cells. In the current study, the effect of boron on cryopreservation of human lung cancer cell line, A549, and murine fibroblast cell line, L929, was investigated with the help of cell viability assay, colony forming unit assay and RT-PCR analysis. 15 µg/ml boron supplemented freezing medium was found to indicate a positive effect on cell viability. Moreover, gene expression profiles of A549 and L929 cell lines have been altered. The levels of apoptosis related genes decreased while proliferation related gene levels increased significantly after repeated freeze-thaw cycles or long period of freezing. As indicated through our results, sodium pentaborate pentahydrate, as a boron source, might be a crucial cryoprotective agent for cryo-protection and bio-banking of cancer and healthy cells while keeping their viability and functionality.Canlı hücrelerin uzun süre boyunca çok düşük sıcaklıklarda saklanması işlemi kriyo-korunma olarak adlandırılır. Kriyo-koruma işlemi biyoteknoloji, klinik çalışmalar ve hayvan veya bitki hücreleriyle ilgili birçok çalışmada çok önemli bir rol oynadığından dolayı, kriyo-korumada kullanılan ajanların araştırılması son derece mühimdir. Kriyo- koruma ajanları, hücresel metabolizma ve biyofizyoloji üzerindeki etkileri nedeniyle uzun süreli kriyo-korumanın ardından hücresel canlılığın korunmasını sağlarlar. Mevcut çalışmada; hücre canlılık testi, koloni oluşturma testi ve gerçek zamanlı polimeraz zincir reaksiyonu tekniklerinden yararlanılarak, borun kriyo-koruma üzerindeki etkisi, insan akciğer kanser hücre hattı, A549 ve fare fibroblast hücre hattı, L929 kullanılarak araştırılmıştır. Hücre dondurma ortamını 15 µg/ml bor ile desteklemenin hücre canlılığı üzerine olumlu etki ettiği gözlemlenmiştir. Ayrıca, tekrar eden dondurma - çözme döngüleri ve uzun süreli kriyo-koruma sonucunda, gen anlatım profilleri değişen A549 ve L929 hücre hatlarının, bor takviyesi sonrasında, programlı hücre ölümüyle alakalı genlerinin anlatımında azalma, hücre çoğalması ile ilgili genlerinde de artış gözlemlenmiştir. Sonuçlarımız göstermiştir ki bor kaynağı olarak sodium pentaborat pentahidrat, kanser veya sağlıklı hücrelerin canlılıklarını kaybetmeksizin dondurulmalarını ve hücrelerin uzun süreli saklanmaları için son derece önemli bir kriyo-koruyucu ajan olarak kullanılabilir

Design and synthesis of phenylpiperazine derivatives as potent anticancer agents for prostate cancer

Dogan, Aysegul/0000-0003-4160-2270; demirci, serpil/0000-0002-6579-4273WOS: 000486930200001PubMed: 31148379Novel thiourea (5a, 5b) and thiazolidinone derivatives (6a, 6b) were synthesized by hybridizing molecules starting from the compound 6-(4-phenylpiperazin-1-yl)pyridin-3-amine (4) which is known to show anticancer activity. The synthesis of the leading compound was carried out by using 1-(5-nitropyridin-2-yl)-4-phenylpiperazine (3) which was obtained by a novel method of the reaction of 2-chloro-5-nitropyridine (1) and N-phenylpiperazine (2). The structures of the compounds were confirmed using FTIR, H-1 NMR, C-13 NMR, HRMS spectroscopic methods and elemental analysis. The organic molecules were tested for their anticancer activities against prostate cancer (PC) cell lines: DU 145, PC-3 and LNCaP. As the compound 5a exerted the highest cytotoxic activity, IC50 concentrations of compound 5a were further investigated in terms of morphology, colony-forming ability, RNA expression, fragmented DNA and cell cycle distributions of PC cell lines. Overall data revealed that compound 5a treatment induces apoptosis and DNA fragmentation in PC cell lines and inhibits cell cycle progression resulting in the accumulation of cells in either the G1 or the S phases

Synthesis, Molecular Docking and Anticancer Activity of Diflunisal Derivatives as Cyclooxygenase Enzyme Inhibitors

Cyclooxygenase enzymes play a vital role in inflammatory pathways in the human body. Apart from their relation with inflammation, the additional involvement of COX-2 enzyme with cancer activity was recently discovered. In some cancer types the level of COX-2 enzyme is increased indicating that this enzyme could be a suitable target for cancer therapy. Based on these findings, we have synthesized some new diflunisal thiosemicarbazides and 1,2,4-triazoles and tested them against androgen-independent prostate adenocarcinoma (PC-3), colon carcinoma (HCT-116), human breast cancer (T47D), breast carcinoma (MCF7) and human embryonic kidney (HEK-293) cell lines. Specifically, the diflunisal and thiosemicarbazide functionality are combined during the synthesis of original compounds anticipating a potency enhancement. Compounds 6, 10, 15 and 16 did not show cytotoxic effects for the HEK293 cell line. Among them, compounds 15 and 16 demonstrated anticancer activity for the breast cancer cell line T47D, whereas compounds 6 and 10 which are thiosemicarbazide derivatives displayed anti-tumourigenic activity against the PC-3 cell line, consistent with the literature. However, no activity was observed for the HCT-116 cancer cell line with the tested thiosemicarbazide derivatives. Only compound 16 displayed activity against the HCT-116 cell line. Therefore, it was speculated that the diflunisal and thiosemicarbazide functionalities potentiate anticancer activity on prostate cancer and the thiosemicarbazide functionality decreases the anticancer activity of diflunisal on colon cancer cell lines. In order to gain insight into the anticancer activity and COX-2 inhibition, molecular docking studies were carried out for COX-1 and COX-2 enzymes utilizing the newly synthesized compounds 15, and 16. Both 15 and 16 showed high selectivity and affinity toward COX-2 isozyme over COX-1, which is in agreement with the experimental results