In silico and in vitro studies of Tyr-Lys-Thr tripeptide against human lung cancer cell line (A549).

Objectives: The main purpose of this study is to predict the effect of Tyr-Lys-Thr (YKT) tripeptide, recognized for its anticancer properties, on lung cancer through theoretical and experimental analyzes.

Background: Peptides are important therapeutic compounds that have been studied for many years. Among these, YKT tripeptide emerges as a significant therapeutic peptide, exhibiting cytotoxic effects on various cancer cell lines.

Methods: The study investigated the involvement of the PI3K/Akt/mTOR pathway, commonly activated in human cancer, and the pivotal role of caspases in apoptosis. The interactions of YKT tripeptide with mTOR, Akt, PI3K, caspase-3, and caspase-8 were investigated through the molecular docking method. Additionally, MTT test was used to determine the cytotoxic activity of YKT against the A549 cell line across concentrations set at 0.1, 0.25, 0.5, 1, 2.5 and 5 mg/mL for 24 and 48 h.

Results and conclusion: In silico docking studies were conducted with PI3K, Akt1, and mTOR, known to be active in human cancer, as well as caspase-3 and caspase-8, key enzymes in apoptosis. It was determined that YKT exhibited a robust binding tendency with each receptor. YKT tripeptide was also found to have a cytotoxic effect on human lung carcinoma cell line A549 (Tab. 5, Fig. 11, Ref. 28).