Determination of the role of routine as a flavonoid in TLR4/TRİF/İRF3 signal path activation on hormone-sensitive breast cancer cells

INTRODUCTION AND OBJECTIVE: Although breast cancer is the second most common malignant neoplasm worldwide, the treatment of the disease is limited due to various clinical features and toxic side effects of chemotherapeutics. Therefore, it is important to evaluate the effects of new therapeutic compounds in breast cancer. Toll-like receptor 4 (TLR4) is one of the most important members of the Toll-like receptor family, and its overexpression in breast cancer cells is associated with progression. Rutin (RUT) is a polyphenolic flavonoid that draws attention in cancer immunotherapy due to its anti-neoplastic activities. Therefore, in this study, it was aimed to investigate the role of RUT in TLR4/TRIF/IRF3 signaling pathway activation in hormone-sensitive breast cancer cells. METHODS: The cytotoxicity of RUT concentrations in MCF-7 cells was determined by WST1 analysis, TLR4 expression level was determined by RT-PCR analysis, cellular localization of TLR4 and IRF3 was determined by IF staining and its anti-migratory effect was determined by Strach assay. RESULTS: It was determined that RUT decreased the viability and migration of MCF7 cells, increased typical apoptotic morphology, suppressed TLR4 expression, decreased endosomal localization of TLR4 and nuclear translocation of IRF3. CONCLUSION: In the study, it was revealed that RUT may mediate TLR4/TRIF/IRF3 signaling pathway by showing anti-inflammatory activity and antagonist activity against TLR4 in hormone sensitive breast cancer. Moreover, more in vitro research is needed to elucidate the cell cascade in which RUT and TLR activation may be involved. Key Words: Apoptosis, breast cancer, flavonoid, rutin, TLR4