Targeting the AKT Pathway as a Therapeutic Strategy for Hepatocellular Carcinoma

Oluseyi Adeboye Akinloye, Adewumi Kamarudeen Aremu, Ibukun Dorcas Akinloye, Jacob Kehinde Akintunde, Antiya Moses Ceaser and Olajire Moshood Olaniyi
Additional contact information
Oluseyi Adeboye Akinloye: Department of Biochemistry, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria
Adewumi Kamarudeen Aremu: 1Department of Biochemistry, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria Department of Basic Science, Kwara State College of Education, Oro, Kwara State, Nigeria
Ibukun Dorcas Akinloye: Department of Biochemistry, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria
Jacob Kehinde Akintunde: Department of Biochemistry, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria
Antiya Moses Ceaser: Department of Biochemistry, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria
Olajire Moshood Olaniyi: Department of Veterinary Pathology, Federal University of Agriculture, Abeokuta, Ogun State, Nigeria

International Journal of Research and Scientific Innovation, 2024, vol. 11, issue 11, 38-45

Abstract: Hepatocellular carcinoma (HCC), one of the most common cancers of the liver has been on the rise globally and is complicated by drug resistance in treatment targets and pathway interactions such as the Akt pathway. Akt-1 protein also known as serine/threonine kinase is a good target for designing drugs for hepatocellular carcinoma. It controls cell development, survival, proliferation, glycogen consumption, and apoptosis. The overexpression of Akt-1 is a hallmark of various cancers including HCC, and plays a crucial role in tumorigenesis and cancer progression. The 3D crystal structure of human Akt-1 with an allosteric inhibitor was downloaded from a protein data bank. The preparation of ligands was done by downloading structures from the PubChem database and converted to 3D using Open Babel. In this study, phytochemicals (ligands) from some Nigerian medicinal plants were docked against the binding pocket of Akt 1 using virtual high throughput screening. Validation of docking results was done to determine the accuracy of the docking methods. The drug-like properties of the lead compounds and the standard drug were tested by employing the Lipinski rule of five. Silymarin has the highest docking score of -10.6 kcal/mol and was found to be the lead compound as a potential inhibitor with the best absorption, distribution, metabolism, and excretion properties. Silymarin interactions with key amino acid residues in the active sites were determined and compared with the reference drug, sorafenib. It was found that both silymarin and sorafenib exhibit similar interactions with the formation of hydrogen bonds, pi-cation, and pi-pi interactions. Silymarin has a relatively better inhibitory and pharmacokinetic profile than, vicenin, epig allocate chin-3-gallate, ginsenoside, and palstatin, thus it can be a useful therapeutic candidate in the treatment of HCC.

Date: 2024
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.rsisinternational.org/journals/ijrsi/d ... 1-issue-11/38-45.pdf (application/pdf)
https://rsisinternational.org/journals/ijrsi/artic ... ocellular-carcinoma/ (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:bjc:journl:v:11:y:2024:i:11:p:38-45

Access Statistics for this article

International Journal of Research and Scientific Innovation is currently edited by Dr. Renu Malsaria

More articles in International Journal of Research and Scientific Innovation from International Journal of Research and Scientific Innovation (IJRSI)
Bibliographic data for series maintained by Dr. Renu Malsaria ().