Background: Piperine, an amide extracted from the Piper spices, exhibits strong anti-tumor properties. However, its effect on the epithelial–mesenchymal transition (EMT) process has never been investigated. Herein, we evaluate the toxic effect of piperine on lung adenocarcinoma (A549), breast adenocarcinoma (MDA-MB-231) and hepatocellular carcinoma (HepG2) cell lines, as well as its ability to inhibit EMT-related events induced by TGF-β1 treatment. Methods: The cell viability was investigated by MTT assay. Protein expression was evaluated by Western blot. Gene expression was monitored by real-time PCR. Zymography assay was employed to detect metalloproteinase (MMP) activity in conditioned media. Cell motility was assessed by the wound-healing and phagokinetic gold sol assays. Results: The results revealed that piperine was cytotoxic in concentrations over 100 µM, showing IC50 values for HepG2, MDA-MB-231 and A549 cell lines of 214, 238 and 198 µM, respectively. In order to investigate whether piperine would reverse the TGF-β1 induced-EMT, the A549 cell line was pretreated with sublethal concentrations of the natural amide followed by the addition of TGF-β1. Besides disrupting EMT-related events, piperine also inhibited both ERK 1/2 and SMAD 2 phosphorylation. Conclusions: These results suggest that piperine might be further used in therapeutic strategies for metastatic cancer and EMT-related disorders.
Hepatitis C treatment with interferon alpha-2b (IFN-alpha) and ribavirin has been related to decreased bone mineral density. The aim of this study was to investigate the in vitro effects of different concentrations of ribavirin and IFN-alpha on osteoblast-like cells. Human osteoblast-like cells obtained by the outgrowth of cells from bone chips were exposed to ribavirin (0.1-10 microg/mL) or IFN-alpha (0.1-1000 UI/mL). At regular time-points, cultures were harvested for posterior analysis. Alkaline phosphatase (ALP) activity was determined on days 7 and 14, and cell growth was accessed by C3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and cell count on days 1, 3, 5, and 7. Flow cytometry analysis was used for investigating cell death on days 1, 3, 5, and 7. IFN-alpha affected ALP expression only at the higher concentration (1000 UI/mL) after 7 days (P < 0.05). No effects were detected in cell growth. In ribavirin treated cultures, concentrations higher than 2.5 microg/mL were associated with a decrease in ALP activity within 7 and 14 days (P < 0.01 and P < 0.001, respectively). Furthermore, the reduction in cell growth was dose-dependent and was detected after the fifth day. This decrease can be explained by an increase in the number of dead cells and a decrease in cell proliferation. In conclusion, our experiments demonstrated that ribavirin reduced, in a time- and dose-dependent manner, the number of metabolically active cells through a decrease in proliferation and an increase in cell death, and induced an impairment in osteoblast differentiation. These negative effects of ribavirin on osteblast-like cells might contribute to the bone loss reported in vivo.
Coronavirus disease 2019 (COVID-19) can progress to severe pneumonia with respiratory failure and is aggravated by the deregulation of the immune system causing an excessive inflammation including the cytokine storm. Since 2019, several studies regarding the interplay between autoimmune diseases and COVID-19 infections is increasing all over the world. In addition, thanks to new scientific findings, we actually know better why certain conditions are considered a higher risk in both situations. There are instances when having an autoimmune disease increases susceptibility to COVID-19 complications, such as when autoantibodies capable of neutralizing type I IFN are present, and other situations in which having COVID-19 infection precedes the appearance of various autoimmune and autoinflammatory diseases, including multisystem inflammatory syndrome in children (MIS-C), Guillain-Barré syndrome, and Autoimmune haemolytic anaemia (AIHA), thus, adding to the growing mystery surrounding the SARS-CoV-2 virus and raising questions about the nature of its link with autoimmune and autoinflammatory sequelae. Herein, we discuss the role of host and virus genetics and some possible immunological mechanisms that might lead to the disease aggravation.
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