Investigation of the effects of isoindol derivative compounds on multi-drug resıstance and apoptotic signaling pathways in human breast and colon cancer cells

Heterocyclic compounds, constituting an important class of organic chemistry, are compounds with known anticarcinogenic, anti-inflammatory, antiviral and antiallergic properties that can be easily derivatized with other drug active compounds. According to the literature reviews, although there are many studies on the application of heterocyclic compounds in different disciplines, biological activity studies related to different derivatives of this compound are rare. Cancer disease is expressed as unregulated DNA replicating itself and cell division. Today, it is one of the most important health problems and different methods are used for its treatment (surgical intervention, chemotherapy, immunotherapy, gene therapy, radiotherapy and photodynamic therapy, etc.). New treatment strategies are needed because effective treatment methods are not sufficient for cancer types while developing anticarcinogenic drugs. In this study; In MCF-7 (breast cancer), MCF-12A (normal breast epithelium) and DLD-1 (colon cancer), CCD-18Co (normal colon epithelium) cell lines, the cytotoxic dose and IC50 value of heterocyclic compounds were determined by MTT method; The effect on cell viability will be determined by the real-time cell analysis system (RTCA). In the indicated cell lines of the compounds whose IC50 values were determined; The effect of cell cycle and apoptosis will be evaluated by flow cytometry method depending on the concentration and time (PI staining and AnnexinV / PI dual staining). After determining the presence of apoptosis, it is aimed to perform gene and protein expression analyzes that are involved in signal pathways to be associated with apoptosis. The anti-carcinogenic effects of heterocyclic compounds, the mRNA levels of the pump proteins ABCB1 (MDR1-P-gp), ABCC3 (MRP3), ABCC10 (MRP7), ABCC11 (MRP8) and ABCG2 (BCRP), which play an important role in chemotherapy resistance, were determined by RT-PCR method. It will be. In addition, proteins involved in apoptosis and related signaling pathways; BAD, BAX, BCL2, BCL2L11, BCL2L2, BID, BIRC3, BIRC5, BIRC7, CASP3, CASP8, CD40, CD40LG, CDKN1A, CDKN1B, CYCS, DIABLO, FAS, FASLG, HSPA14, HSPA4, HSPB1, HTRA2 IGF2, IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, IGFBP6, LTA, TNF, TNFRSF10A, TNFRSF10B, TNFRSF10C, TNFRSF10D, TNFRSF1A, TNFRSF1B, TNFRSF21, TNFRSF1B, AKTRSF21, TNFRSF1B, The quantities of EIF2A, MAP3K7, MAPK1, MAPK3, MAPK8, NFKBIA, PARP1, PSMD9, REL-A, SMAD2 will be measured with the membrane-associated protein array kit.