Targeting PI3K/AKT/mTOR signalling pathway in non-small-cell lung carcinoma: Exploring promising bioactive natural compounds as anti-cancer agents

Abstract

Lung cancer has become the most common solid tumor and the leading cause of cancer-related deaths worldwide. It is estimated that the annual mortality rate for lung cancer is 1.8 million out of which 85 % are non-small-cell lung cancer (NSCLC) cases. PI3K/Akt/mTOR signalling pathways play a critical role in both pathological and physiological situations, influencing different aspects of cell survival and proliferation in lung cancer. Despite the use of several therapies, lung cancer treatment has been found to be insufficient, leading to unsatisfactory patient outcomes. There has been a growing interest in natural compounds derived from plants, due to their easy availability, low toxicity, cost-effectiveness, and ability to regulate various biological pathways. Therefore, in the current investigation, we studied various natural compounds having an inhibitory action on PI3K/Akt/mTOR signalling pathways in lung cancer by inducing apoptosis. Further, natural compounds like vitexin, betalain, morusin, bromophenol erianin, peruvoside, and resveratrol were found to decrease Bcl-2 and Bcl-xl expression, whereas elevated BAX, caspase-3, caspase-7, and caspase-9 expression leading to apoptosis and downregulation of p-PI3K/p-Akt/p-mTOR expression in NSCLC.The ultimate goal is to create new and safe treatments for the prevention and treatment of lung cancer.

Keywords

• Lung cancer
• PI3K/Akt/mTOR signalling pathway
• Natural compounds
• Cell apoptosis
• Autophagy
• PTEN