Potential inhibitory action of cafestol on apoptosis proteins: An in-silico study

Abstract

Coffee has been found to reduce cell proliferation and induce apoptosis, which is significant in terms of protecting against cancer. However, the molecular mechanism of this effect is yet to be fully elucidated. The aim of this study was to evaluate the affinity between 12 key proteins involved in apoptosis and four of the main compounds derived from coffee: caffeine, cafestol, caffeic acid, and chlorogenic acid, in order to contribute to the understanding of the effect of coffee on apoptosis. Molecular docking was performed between proteins and ligands using Autodock Tools in Autodock Vina. The best protein-ligand complexes were then submitted to molecular dynamics (MD) simulations in GROMACS 2018.2. The best interactions in molecular docking analysis were Bcl-2 with cafestol, Bcl2l1 with cafestol, and Bax with cafestol. MD simulations show that cafestol binds more strongly within the binding pockets of Bcl-2 and Bax, while the Bcl2l1-cafestol complex is not very stable. These results imply that cafestol competes for binding with Bcl-2 and Bax. Binding of cafestol could inhibit the anti-apoptotic activity of Bcl-2 and promote the pro-apoptotic activity of Bax, thus favoring apoptosis. This is especially relevant in the context of cancer cells, where the expression of Bcl-2 can be increased. We propose a model in which the binding of cafestol with Bcl-2 favors a pro-apoptotic effect, and as such is worth further scrutiny as an anticancer strategy.