Dual inhibitory effects of novel naringenin analogue in tobacco-carcinogen induced lung cancer via inhibition of PI3K/Akt/mTOR pathway

Abstract

Background: Phosphoinositide 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) pathways is considered as the signalling pathway which activates the diverse cellular function viz., survival, cell expansion, vesicular transport and proliferation and found frequently dysregulated pathway in lung cancer. Consequently flavonoids based inhibitors play a key kinase role in the pathway including mTOR PI3K and AKT, have been extensively scrutinized in targeting the oncology in recent years. The common pathway to PI3K-Akt-mTOR used to target during the lung cancer therapy. Therefore, the current study was aimed to peruse the naringenin as dual PI3K/mTOR for lung cancer. Methods: In the current experimental study mice were randomly divided into 7 groups with 12 mice in each groups The oxidative stress was evaluated in term of antioxidant parameters such as myeloperoxidase (MPO) and superoxide dismutase (SOD), respectively. The proinflammatory cytokines viz., interleukin (IL)-1b, tumor necrosis factor-a (TNF-a) and interleukin (IL)-6 were measured via using the standard enzyme-linked immunosorbent assay kits. The concentration of PI3K, P-PI3K, mTOR P-mTOR Akt and P-Akt were determined via using the Western blot techniques. We also performed the histopathological study to identify the changes during the disease. Results: Naringenin significantly suppressed the oxidative stress via improving the status of endogenous antioxidant parameters such as SOD and MPO in a dose dependent manner. disease control group mice confirmed the change in protein levels of PI3K/Akt/mTOR pathway in lung as compared to normal control, which were significantly down-regulated by the naringenin in a dose dependent manner. In the histological study, we observed that the naringenin substantially reduced the benzopyrene induced neutrophils in lung tissue. Conclusions: It can be concluded that naringenin has shown promising anticancer effect via attenuation of PI3K/Akt/mTOR against lung cancer and signifies the potential therapeutic relevance for further development.