The effects of Sideritis akmanii on endoplasmic reticulum stress, inflammation, and DNA damage in experimentally ER-stress-induced MCF-7 cancer cells
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Keywords:MCF-7, ER-stress, Comet assay, Sideritis akmanii, Cytotoxicity, Genotoxicity
Cancer is one of the diseases that became a social problem that can happen with uncontrolled proliferation, growth, differentiation, and spread of cells in our body. Breast cancer, on the other hand, is one of the types of cancer with the highest incidence in women. In our study, endoplasmic reticulum (ER) stress is induced by thapsigargin (T) in MCF-7 cells and then, the effects of Sideritis akmanii acetone extract (SAE) on cell viability, ER stress, inflammation, and DNA damage were investigated. The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] test was used to determine the effect of SAE on cytotoxicity and the comet (SCGE; single-cell gel electrophoresis) assay was used for the effects on genotoxicity. Additionally, the mRNA expression levels of both ER stress parameters (ATF4: activating transcription factor 4, ATF6: activating transcription factor 6, PERK: protein kinase RNA-like ER kinase, GRP78: glucose-regulated protein 78) and inflammation-related parameters (TNF alpha: tumor necrosis factor-alpha, IFN-gamma: interferon-gamma, IL-6: interleukin-6, IL-8: interleukin-8, IL-12: interleukin-12) were determined by qPCR. The results showed that DNA damage levels increased as a result of T treatment, DNA damage caused by T decreased when a low dose of SAE was administered and a high dose of SAE further increased DNA damage levels. It was determined that SAE, administered in different doses with T or alone in experimental groups, increased mRNA expression levels of all ER stress and inflammatory genes compared to the control group. As a result, it has been determined that S. akmanii, especially at high doses, may exhibit anticarcinogenic effects through its effects on genotoxic, cytotoxic, and ER stress in MCF-7 cells.
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