Investigation of Apoptotic Effect of Klotho Protein on Human Colorectal Cancer Cells via TRAIL Death Receptors

Abstract

Klotho is a transmembrane protein which is deficiency has pleiotropic effects in a number of aging-related disease processes and various cancers. In some recent studies about klotho protein disorders, it has been shown to klotho is effective in various cancers including lung, liver, breast, kidney, and colon. TNF-related apoptosis-inducing ligand (TRAIL), a TNF family molecule, is a cytokine that stimulates apoptosis through death receptors in many cancer types and therefore attracts attention for tumor therapies in various preclinical models. Interaction with TRAIL death receptors create an apoptotic effect in cancer treatments by reducing the proliferation of cancer cells. In this study, it was aimed to investigate the effects of exogen klotho administration on cell viability and apoptosis on TRAIL death receptors (TRAIL1 and TRAILR2) in human healthy colon cells (CCD 841 CoN) and TRAIL-resistant human colorectal cancer cells (caco2). For this purpose, cells were treated with different concentrations of klotho for 24 and 48 hours. To determine the cell viability, proliferation, and death receptors effects of klotho protein on cancer and healthy cells evaluations with WST-8 and Real-Time qRT-PCR analysis were performed. Our results showed that the increase in klotho protein concentration did not have a significant effect on cell viability in healthy colon cells, whereas it decreased cell viability and proliferation in apoptosis-resistant human colorectal cancer cells. Relative gene expression of TRAIL1 and TRAILR2 death receptors increased with klotho applied to the apoptosis-resistant colorectal cancer cell line caco-2. Therefore, targeting the ligand-receptors that induce TNF-related apoptosis with the klotho protein can be considered as a potential therapeutic approach for cancer therapy.