The Dark Side of IFN-γ: Its Role in Promoting Cancer Immunoevasion

Interferon-γ (IFN-γ) is a pleiotropic cytokine that has long been praised as an important effector molecule of anti-tumor immunity, capable of suppressing tumor growth through various mechanisms. On the contrary to such a bright side of IFN-γ, it has also been involved in promoting an outgrowth of tumor cells with immunoevasive phenotype suggesting an existence of a dark “tumor-promoting” side effect of IFN-γ. In this review, we will summarize this multi-functional role of IFN-γ in tumor context, how it promotes changes in tumor phenotype towards increased fitness for growth in immunocompetent host. Furthermore, we summarize how IFN-γ is involved in homeostatic or cancer-triggered mechanisms to establish an immunosuppressive tumor microenvironment

Alpha-1-Antitrypsin Antagonizes Cisplatin-Induced Cytotoxicity in Prostate Cancer (PC3) and Melanoma Cancer (A375) Cell Lines

Increased circulating alpha-1-antitrypsin (AAT) correlates with cancer stage/aggressiveness, but its role in cancer biology is unclear. We revealed antagonistic effect of AAT to cisplatin-induced cytotoxicity in prostate (PC3) and melanoma (A375) cancer cell lines. Moreover, AAT abrogated cytotoxicity of MEK inhibitor U0126 in PC3 cell line. Weaker antagonistic effect of AAT on cytotoxicity of PI3/Akt and NF-kB inhibitors was also observed. In addition, cisplatin increased AAT gene expression in transfected PC3 cells. However, AAT derived from transfected PC3 cells did not antagonize cisplatin-induced cytotoxicity. In conclusion, these results suggest possible association between high circulating AAT and cisplatin resistance

ALPHA-1 Antitrypsin Affects U0126-Induced Cytotoxicity in Colon Cancer Cell Line (HCT116)

Alpha-1-antitrypsin (AAT), an acute phase protein, is the principal circulatory anti-protease. This multifunctional protein is encoded by the SERPINA1 gene. Although AAT was recognised as a potential tumour marker, its role in cancer biology remains unknown. Given that it has been demonstrated that AAT has an anti-apoptotic property against non-malignant cells, we aimed to investigate whether AAT affects apoptosis in a colon cancer cell line (HCT116). The presence of AAT in the HCT116 cell culture antagonized cytotoxicity of blockers of MEK1/2, PI3K/Akt pathways as well as NF-kappa B. The dominantly recovered cell viability was observed in the co-treatment with MEK1/2 inhibitor U0126. In addition, it was revealed that AAT almost completely abolished U0126-induced apoptosis through maintenance of the autophagy process. Our study revealed for the first time that the observed cyto-protection triggered by AAT was accompanied by sustained autophagy which opposed apoptosis. These results may contribute to understanding of the role of AAT in cancer development and evaluation of efficacy of cancer therapy

In Vitro Assessment of Ni-Cr and Co-Cr Dental Alloys Upon Recasting: Cellular Compatibility

The aim of this study was to evaluate the effect of recasting of commercially available Ni-Cr (Wiron 99) and Co-Cr (Dentalit C) dental alloys on physiology of microenvironmental cells. The viability of fibrosarcoma (L929) cells, human embrional fibroblasts (MRC-5) and isolated peripheral blood mononuclear cells (PBMC) was measured by MTT and acidic phosphatase tests. Presence of dying cells was estimated by Annexin/PI staining while the production of intracellular nitric oxide (NO), reactive oxygen (ROS) and nitrogen (RNS) species was determined by DAF-FM diacetate and DHR staining. Recasting of Ni-Cr alloy intensified its cytotoxicity manifested through enhanced free radicals production, induction of cell death and permamently diminished cell proliferation. On the other hand, after initial toxic effect cells adapted to the presence of Co-Cr alloys. Independently of recasting, Co-Cr alloys are more compatible with microenvironment then Ni-Cr alloy. Oppositely, recasting of Ni-Cr alloy promoted its toxicity

In Vitro Assessment of Ni-Cr and Co-Cr Dental Alloys Upon Recasting: Cellular Compatibility

The aim of this study was to evaluate the effect of recasting of commercially available Ni-Cr (Wiron 99) and Co-Cr (Dentalit C) dental alloys on physiology of microenvironmental cells. The viability of fibrosarcoma (L929) cells, human embrional fibroblasts (MRC-5) and isolated peripheral blood mononuclear cells (PBMC) was measured by MTT and acidic phosphatase tests. Presence of dying cells was estimated by Annexin/PI staining while the production of intracellular nitric oxide (NO), reactive oxygen (ROS) and nitrogen (RNS) species was determined by DAF-FM diacetate and DHR staining. Recasting of Ni-Cr alloy intensified its cytotoxicity manifested through enhanced free radicals production, induction of cell death and permamently diminished cell proliferation. On the other hand, after initial toxic effect cells adapted to the presence of Co-Cr alloys. Independently of recasting, Co-Cr alloys are more compatible with microenvironment then Ni-Cr alloy. Oppositely, recasting of Ni-Cr alloy promoted its toxicity