Investigation of cytotoxic and apoptotic activities of cyclotriphosphazene derivative compounds on colon cancer cells

Colorectal Cancer (CRC), which ranks third among cancer types in terms of incidence and mortality worldwide, is seen as an important health problem. The treatment process of this cancer type becomes difficult due to its diagnosis, especially at a late stage. The effects of parabens, which are widely used in the cosmetics and food industry, on cancer development are being investigated more. Phosphazenes, which have a P–N skeleton, can be easily functionalized with various organic groups, and exhibit high biocompatibility and anticancer potential, have attracted attention in recent years, especially in drug delivery systems and targeted therapies. Studies have shown that these structures can exhibit significant cytotoxic and apoptotic effects in colorectal and breast cancer cell lines. In this study, it was aimed to investigate the cytotoxic and apoptotic effects of aniline-derived cyclotriphosphazene and aniline-paraben-derived cyclotriphosphazene compounds in Caco-2 (human colon adenocarcinoma) and CCD-18Co (normal colon fibroblast) cell lines. The effects of these compounds on cell viability were determined by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5 Diphenyltetrazolium Bromide) analysis, and the mRNA levels of BAX, BCL-2 and KASPAZ-3 genes, which are molecular markers of apoptotic mechanisms, were determined by qRT-PCR (Real Time Polymerase Chain Reaction). It was determined that cell viability decreased and cytotoxic effect was observed in the Caco-2 cell line depending on the dose. IC₅₀ values were calculated in the range of 11.67 μM for compound-3 and 16.62 μM for compound-5. It was observed that there was a significant increase in BAX and KASPAZ-3 gene expression levels and a significant decrease in BCL-2 gene. The results obtained suggest that the compounds exhibit cytotoxic and apoptotic activity in colon (Caco2) cancer cells, may have effects on cellular death mechanisms, and may be evaluated as potential anticancer agents.