Involvement of Pca1 in ROS-mediated apoptotic cell death induced by alpha-thujone in the fission yeast (Schizosaccharomyces pombe).

Alpha-thujone, widely used in beverages (1-5 mg/kg), is known to have cytotoxic effects, but the mode of action and the role of potential apoptotic proteins in yeast cell death should be unraveled. In this study, we used Schizosaccharomyces pombe, which is a promising unicellular model organism in mechanistic toxicology and cell biology, to investigate the involvement of pro-apoptotic factors in alpha-thujone-induced cell death. We showed alpha-thujone-induced ROS accumulation-dependent cytotoxicity and apoptosis. In addition, we used superoxide dismutase-deficient cells (sod1 and sod2 mutants) to understand the effect of oxidative stress. Alpha-thujone caused significant cytotoxicity and apoptotic cell death, particularly in sod mutants. Moreover, two potential apoptotic factors, pca1 and pnu1 (pombe caspase-1 and pombe nuc1) were investigated to understand which factor mediates alpha-thujone-induced cell death. Pca1-deficient cells showed increased survival rates and reduced apoptosis in comparison to parental cells after chemical treatment while pnu1 mutation did not cause any significant change and the response was found identical as of parental cells. Yeast responded to alpha-thujone in caspase-dependent manner which was very similar to that for acetic acid. In conclusion, alfa-thujone-induced apoptosis and accounting mechanisms, which were mediated by ROS and driven by Pca1, were clarified in the unicellular model, S. pombe.

DNA Binding and Anticancer Properties of New Pd(II)-Phosphorus Schiff Base Metal Complexes.

DNA has become the target of metal complexes in cancer drug discovery. Due to the side effects of widely known cisplatin and its derivative compounds, alternative metal-based drug discovery studies are still ongoing. In this study, the DNA-binding ability of Pd(II) and Pt(II) complexes of four phosphorus Schiff base ligands and four hydrazonoic-phosphines are investigated by using in silico analyses. Phosphorus Schiff base-Pd(II) complexes encoded as B1 and B2 with the best DNA-binding potential are synthesized and characterized. The DNA-binding potentials of these two new Pd(II) complexes are also investigated experimentally, and their antitumor properties are demonstrated in vitro in A549, MCF7, HuH7, and HCT116 cancer cells. The mechanisms of these metal complexes that kill the cells mentioned above in different activities are elucidated by flow cytometry apoptosis analysis and colony formation analysis The in silico binding energies of these two new palladium complexes ΔG (B1): -4.51 and ΔG (B2): -6.04 kcal/mol, and their experimental DNA-binding constants were found as Kb (B1): 4.24 × 105, Kb (B2): 4.98 × 105). The new complexes, which show different antitumor effects in different cells, are the least effective in HuH7 liver cells, while they showed the best antitumor properties in HCT116 colon cancer cells.

Evaluation of the antitumor activity of a series of the pincer-type metallocomplexes produced from isonicotinohydrazide derivative.

In this work we report on the antitumor properties of a series of pincer-type metallocomplexes [Hg2(HL-keto)Cl4]n (1), [Hg(HL-keto)I2] (2) and [Mn(HL-zwitterion)Cl2]∙MeOH (3∙MeOH), derived from N'-(1-(pyridin-2-yl)ethylidene)isonicotinohydrazide (HL) and corresponding metal salts. The Hg(II) and Mn(II) salts are chelated by the keto (HL-keto) or zwitterionic (HL-zwitterion) form of HL, respectively. The cytotoxic effects of these compounds have been accessed against lung adenocarcinoma (A549) and hepatocellular carcinoma (HepG2 and Huh7) cell lines. Complexes 1 and 2 were found to be most efficient against the cell line Huh7 with IC50 value of 2.56 and 9.90 µM, respectively, while they exhibit moderate activity towards cell lines A549 and HepG2, as evidenced from IC50 values in the range 27.98-56.99 µM. Complex 3∙MeOH is less efficient towards all the three cell lines with relatively high IC50 values. The mechanisms of the metallocomplexes killing the aforementioned cells were elucidated by flow cytometry, colony formation and polymerase chain reaction (PCR) analysis of apoptosis related expression of the genes. The results of the cytotoxic effects and antitumor activity on different cell lines are affected by the metal nature and the presence of the coordinated halide.

COVID-19 patients' sera induce epithelial mesenchymal transition in cancer cells.

Covid-19 Pneumonia of SARS-CoV-2 pandemic infection, persists to have high disease burden especially in cancer patients. Increased inflammation and thromboembolic processes are blamed to influence cancer patients more than the others but due to lack of knowledge regarding the pathophysiology of the both the virus itself and the response of the host, more basic and translational disease modeling research is needed to understand Cancer-Covid-19 interaction. In this study, serum samples from the patients, who were hospitalized due to Covid-19 pneumonia, applied to different cancer cells and cytotoxicity, motility, proliferation and gene expression analysis were performed. Serum samples derived from healthy volunteers and the fetal bovine serum that is used regularly in cell culture experiments used as controls. Hospitalized Covid-19 patients who had also cancer, were retrospectively screened, and their clinical course were recorded. Overall 12 Patient (PS) and 4 healthy serums (CS) were included in the experiments. PS applied cells showed increased motility in A549 cells as well as lost cell to cell connection in MCF7 and HCT116 cells, and induced expression of VIM, ZEB1 and SNAIL2 mRNA levels. Eight cancer diagnosed patients who were hospitalized due to Covid-19 between April and September 2020 were also reviewed retrospectively, which 5 of them were dead during SARS-CoV-2 infection. Thorax CT images of the 2 patients showed increased metastatic nodules in the lungs as of January 2021. The results of the study indicate that metastasis may be one of the prolonged consequences of COVID-19 pandemic in cancer sufferers.