Investigation of the paracrine effects of luteolin against breast cancer cells and agi̇ng-related secretory phenotype

Aging is the sum of structural, functional and psychological changes in the organism, regulated by a genetic program and influenced by environmental factors. It is the major risk factor for a number of diseases associated with advancing chronological age. Studies on the relationship between aging and cancer suggest that aging cells accumulate in tissues and lead to degeneration with aging. Therefore, interventions in the basic aging process hold promise for curing many age-related diseases, especially cancer. One of the hallmarks of the basic aging process is cellular senescence. Cellular senescence is a multifaceted stress response adopted by dividing cells. In vivo studies have shown that a complex mechanism involving a variety of cytokines, chemokines, growth factors and proteases leads to the formation of an aging-associated secretory phenotype (SAPS), which results in an irreversible arrest of cell proliferation. In studies conducted to identify regulatory molecules that can suppress the secretory phenotype (SAPS), some flavonoids have been identified as secretory phenotype (SAPS) inhibitors through IL-6, an important SAPS component. This supports the idea that this flavonoid group may suppress the aging process and regulate signal transduction pathways. Luteolin is widely found in many plant species. It has been shown to be a flavonoid that can block many points in the progression of carcinogenesis, including metastasis, apoptosis and angiogenesis on the cell. Considering the structure of luteolin in the literature, the cellular pathways it affects and its effects on tumor development, the hypothesis that it is associated with the SAPS phenotype has been raised. Within the scope of the project, it was aimed to show the extent to which luteolin flavonoid suppresses the secretory phenotype (SAPS), which is a stress response associated with proliferation and aging, on breast cancer cells. For this purpose, an aged fibroblast cell model will be established in the study. Then, the paracrine effects of these cells on breast cancer cells will be examined. In these cells treated with luteolin, it is aimed to show that by regulating the IL-6/NF-κB signal transduction pathway, the secretory phenotype can be suppressed and the proliferation and migration characteristics of cancer cells can be inhibited.