Identifying Biomolecular Targets of the Anticancer Vitamin-E-δ-Tocotrienol Using a Computational Approach: Virtual Target Screening

Author Info

Yuri Pevzner Elza Pevzner Kenyon G. Daniel Wayne C. Guida Wesley H. Brooks Mokenge P. Malafa

Corresponding Author

Wesley H. Brooks
Department of Chemistry, University of South Florida, Tampa, Florida, USA

A B S T R A C T

In recent years, evidence has mounted that a particular form of vitamin E (its δ-tocotrienol variant) may have cellular functions beyond that of an antioxidant, a role commonly ascribed to the tocotrienol class of compounds. In particular, numerous studies of δ-tocotrienol’s effect on cancer cells have identified it as a potent anticancer and antitumor agent. However, this important revelation of potential therapeutic use poses a series of new challenges, with arguably the most important being the elucidation of the precise mechanism of action responsible for the anticancer activity of δ-tocotrienol. As an initial step to address this question, we have used a computational tool, Virtual Target Screening (a molecular docking-based tool that identifies potential binding partners for small molecules), to identify potential biomolecular targets of δ-tocotrienol. Then, to gain a consensus as to the type of biomolecular entity that could be a target for δ-tocotrienol, we utilized PharmMapper and PASS (a ligand-based chemoinformatic approach), and ProBiS (a tool that analyses binding site similarities across known proteins). The results of our multipronged computational consensus-seeking approach showed that such a strategy can identify potential cellular targets of small molecules. This is evidenced by our identification of estrogen receptor-beta, a protein that has been previously shown to bind δ-tocotrienol, which elicited a cellular response. This study supports the use of such a computational approach as an initial step in target identification to avoid time-consuming, costly large-scale experimental screening, greatly reducing the experimental work to just one or a few candidate proteins.

Article Info

Article Type

Research Article

Publication history

Received: Wed 15, Jul 2020
Accepted: Tue 28, Jul 2020
Published: Wed 30, Dec 2020

Copyright

© 2023 Wesley H. Brooks. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Hosting by Science Repository.
DOI: 10.31487/j.COR.2020.08.12