Breast cancer is the most frequently diagnosed cancer among women worldwide. 1 The incidence of breast cancer in Iran is about 20 new cases per 100 000 women-years. 2 This cancer often leads to complete removal of breast tissue, chemotherapy, radiotherapy and hormonotherapy. 3 Several internal and external factors contribute to the development of this cancer. Internal factors such as age, hormonal effects, lifestyle, obesity, alcohol consumption, smoking, gender, anxiety and stress, genetic predisposition (mutation in BRCA1, 2 and other genes) and family history of breast cancer. 4,5 Exogenous factors include infection with oncogenic viruses such as mouse mammary tumor virus (MMTV), human papilloma virus (HPV) and Epstein-Barr virus (EBV). Oncogenic viruses are contributing to 20% of human cancers. 6 EBV is a human gamma-1 herpes virus which has a double-stranded DNA genome comprised of approximately 170-kilobases that codes more of 85 genes, belonging to the c herpes virus family. 7,8 EBV is mostly transmitted from the host to another host via saliva and infects over 90% of the world population and remains in the body for life. 9 Breast epithelial cells can be infected with EBV by cell to cell contact. 10 This virus is accepted as a major contributor to 20% Burkitt lymphoma, 50% Hodgkin′s lymphoma, 10% stomach carcinomas and almost all endemic nasopharyngeal carcinoma. 11
One of the major problems caused by repeated subcutaneous insulin injections in diabetic patients is insulin amyloidosis. Understanding the molecular mechanism of amyloid bril formation of insulin and nding effective compounds to its inhibit or eliminate is very important and extensive research has been done on it. In this study, the anti-amyloidogenic and destabilizing effects of the pyrogallol, as a phenolic compound, on human insulin protein were investigated by CR absorbance, ThT and ANS uorescence, FTIR spectroscopy and atomic force microscopy. According to the obtained results, the formation of amyloid brils at pH 2.0 and 50°C was con rmed by CR, ThT, ANS, FTIR assays. Microscopic images also showed the twisted and long structures of amyloid brils. Simultaneous incubation of the protein with pyrogallol at different concentrations reduced the intensities of CR, ThT and ANS in a dose-dependent manner and no trace of brillar structures was observed in the microscopic images. FTIR spectroscopy also showed that the position of amide I band in the spectrum of samples containing pyrogallol was shifted. Based on the ndings in this study, it can be concluded that pyrogallol can be effective in preventing and suppressing human insulin amyloid brils.
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