Quercetin as a PI3K/Akt Pathway Inhibitor in Hepatocellular Carcinoma: Therapeutic Potential and Drug Delivery Challenges

Abbas Mosad Ajeed; Murtadha Saleh  Jabur

doi:10.51699/cajmns.v7i2.3191

Authors

Abbas Mosad Ajeed Department of Clinical laboratory sciences , Faculty of Pharmacy, Al-Turath University, Baghdad, Iraq
Murtadha Saleh Jabur College of Medicine/Ibn Sina University of Medical and Pharmaceutical Sciences

DOI:

https://doi.org/10.51699/cajmns.v7i2.3191

Keywords:

Hepatocellular Carcinoma, Quercetin, PI3K/Akt Pathway, Targeted Therapy, Nanoparticle Drug Delivery

Abstract

Hepatocellular carcinoma (HCC) is one of the major causes of cancer death globally with most of them being diagnosed late, resistant to treatment and recurring. The phosphoinositide 3-kinase/protein kinase B (PI3K/ Akt) signaling pathway is among the essential molecular mediators of HCC progression and its regulation of the processes of tumor cell proliferation, cell survival, angiogenesis, and metabolic reprogramming. Supernormal induction of PI3K/Akt signaling also leads to an increase in tumor proliferation and response to traditional chemoproteomics. Quercetin, which is a common flavonoid present abundantly in fruits and vegetables, has been discovered as an effective anticancer agent with multi-targeted molecular properties. The review illustrates the therapeutic value of quercetin as a PI3K/Akt inhibitor in HCC. It has been proven by experimental means that quercetin inhibits PI3K/Akt activation, apoptosis by the regulation of Bcl-2/Bax ratio, mTOR signaling, angiogenesis, as well as, epithelial-mesenchymal transition (EMT). Also, quercetin increases oxidative stress mediated tumor cell death and could sensitize HCC cells to conventional therapies, including sorafenib. Even with these encouraging anticancer effects, their clinical application in practice is still deficient because of low water solubility, bioavailability, and metabolism of the molecules and reduced tumor-targeting ability. In recent times, the development of drug delivery systems, such as nanoparticles, liposomes, polymeric micelles and nanoemulsions, has demonstrated a potential of enhancing quercetin stability, pharmacokinetics and targeted delivery to hepatic tumors. Altogether, quercetin is a strong natural PI3K/Akt-modulator with high therapeutic potential in HCC, but the pharmacokinetic and formulation issues need to be overcome to implement the compound in the clinical setting.

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