The inhibition of DNA methyltransferase-1 enzyme can strongly decrease the capacity of cells to enhance the tumour-genesis process. Members of the Estrogen-Related Receptors family regulate several elements of cellular metabolism. These are orphan nuclear receptors that regulate a wide range of functional gene networks involved in breast carcinogenesis and the regulation of associated methionine and folate cycles, providing a proven direct relationship to DNA methylation as a result. Moreover, dietary phytochemicals, such as Curcumin, can involve epigenetic modification, which may decrease the development of many types of cancer, especially breast cancer in women. We conducted this study to investigate the effect of Curcuma (PubChem ID: 969516) on the epigenetic modification and inhibition of the DNA methyltransferase-1 (PDB ID: 3PTA) activity and Estrogen-Related Receptors (PDB ID: 1XB7) using Molecular docking approach and computational tools that may inform whether the Curcuma could provide this protective anticancer effect or not. Interestingly, the DNA methyltrasferase1-Curcumin and Estrogen-Related Receptors-Curcumin complexes display a docking score of -6.9 and -7.1 kcal/mol, respectively. Furthermore, Curcumin displays hydrogen, Pi-Cation, Pi-Anion and Van der Waals bonds with active site residues of the targeted molecules. By targeting DNA methylation via the combined inhibition of estrogen-related receptors and DNMT1, our research opens up a new therapeutic path for breast cancer treatment.Keywords: curcumin, breast cancer, epigenetic, molecular docking, treatment.
Although the widespread of early screening and advanced medical therapies, the breast cancer incidence rate continues to rise among Algerian women. This retrospective study investigated mammary lesions’ epidemiological profile and histopathological characteristics and evaluated primary invasive breast cancer prognostic factors. We found that the incidence of breast cancer increases in middle- aged women between 40 and 60 years. Scarff Bloom Richardson grade II predominates in invasive breast cancer samples. In this study, molecular profiling shows that 82.1% of invasive tumours are hormone receptor-positive. A significant correlation is observed between the age of the patient and the SBR grade (p = 0.001) and with the hormone receptor expression (p = 0.001). In addition, the tumour grade is significantly correlated to oestrogen and progesterone receptor expression (p = 0.000; p = 0.000, respectively). Twenty-two per cent of cases were human epidermal growth factor receptor 2-positive. The Ki-67 proliferation index is expressed in 91% of breast cancer patients and was significantly associated with Scarff Bloom Richardson grade (p = 0.030), the progesterone receptor expression (p = 0.029) and with human epidermal growth factor receptor 2-positivity (p = 0.023). Primary breast cancer with a high grade is more frequent (31%) in young women under 40 years old, presenting 17% of our population. In summary, breast cancer patients in Algeria develop an unfavourable profile. Immunohistochemistry assay has played a pivotal role in assessing breast cancer predictive biomarkers improving the tumour behaviour and response to treatment.
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