Effect of phenolic compounds on colon health and cancer cells; In Silico and In Vitro study

Cancer is one of the most important health problems in the world and in our country, after cardiovascular diseases, with high mortality rates. Colorectal cancer (CRC), which is at the top of the list in terms of high mortality rates, is a type of cancer that has severe metastasis and is difficult to respond to treatment except for early diagnosis. Traditional methods used in treatment are inadequate in cancer types with severe metastatic properties such as CRC. The inadequacy of traditional methods suggests that new and alternative treatment methods should be focused on. In recent studies, herbal-based drugs have been developed for CRC cancer treatment and have begun to be used frequently. This new approach, which was developed by taking advantage of the rich content of plants, is carried out especially by phenolic compounds found in the plant content. In this study, P53, BCL-2, MLH-1, HIF, Bax, Caspase-3, APAF-1, Kras, APC and VEGF proteins were obtained from the RCSB database and prepared for molecular docking studies with the AutoDock Vina program, missing atoms were completed and grid definitions were made. 3D structures of natural compounds such as Chlorogenic acid, Ellagic acid, Gallic acid, Hydroxycinnamic acid, Tannic acid, Epicatechin, Catechin, Anthocyanin, Kaempferol, Resveratrol, Quercetin, Hesperidin, Apigenin, Luteolin, Ginkgolide B, Epigallocatechin-3-gallate, Naringenin, Myricetin, Pterostilbene, Genistein, Daidzein, Glycyrrhizin, Rutin, Luteolin-7-O-glucuronide, Chrysin, Ferulic acid, Proanthocyanidin, Flavanone, Pinoresinol and Lariciresinol were obtained from DrugBank and PubChem databases and converted to PDB format, energy minimization was performed and the bonds were made rotatable. Molecular docking studies were performed between all these compounds and all target proteins, binding energies were calculated and the most suitable binding conformations were visualized with the PyMOL program. Tannic acid (TA), which was determined as the phenolic compound with the highest binding energy as a result of molecular docking studies, was evaluated on human colon cancer cell line HT-29 and healthy colon epithelial cell line CCD-18Co under In vitro conditions. In the cytotoxicity analyses, it was determined that tannic acid showed a significant cytotoxic effect with an IC₅₀ value of 37.6 µM on HT-29 cells, whereas it did not significantly affect cell viability on CCD-18Co cells and the IC₅₀ value was above 200 µM. In this context, the data obtained indicate that phenolic compounds determined as a result of a low-cost and rapid preliminary screening by molecular docking method can provide an important preliminary preparation in revealing their anticancer effects at In vitro level. The fact that tannic acid is especially effective against colon cancer and causes minimal damage to healthy cells indicates that this compound may be a potential therapeutic agent candidate. In addition, this study contributes to the development of alternative and targeted new natural compounds in the treatment of colon cancer, while also shedding light on the data missing in the literature on this subject. Keywords: Molecular Docking, Colon Cancer, Cytotoxicity, Phenolic Compounds