Naringenin Sensitizes Lung Cancer NCI‑H23 Cells to Radiation by Downregulation of Akt Expression and Metastasis while Promoting Apoptosis

Abstract

Objectives: The objective of the study was to check for the ability of NGN to promote radiosensitization of the lung cancer cell line – NCI‑H23 (H23).Materials and Methods: 3‑(4,5-dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay, trypan blue exclusion assay, and colony‑forming assay were performed to check the effect of NGN, with and without X‑ray treatment, on the viability of cancer cells. Protein carbonylation, DNA fragmentation, and caspase‑3 activity were determined. The levels of pAkt, Akt, matrix metalloproteinase‑2 (MMP‑2), RAD50, and p21 proteins were looked at by Western blotting. Messenger RNA (mRNA) levels of AKT1, CASPASE3, BAX, BCL2, and BCLXL were also checked.Results: When combined with radiation, NGN lowered the survivability of H23 cells. NGN showed a prooxidant effect while no DNA fragmentation was observed. mRNA levels of CASPASE3 and caspase‑3 activity also showed an increase. pAkt, Akt, MMP‑2, and p21 protein levels were lowered in the NGN‑treated groups, while the RAD50 protein levels showed an increase. The mRNA levels of BCL2 and BCLXL were lowered, while BAX mRNA levels were elevated in response to NGN treatment.Conclusion: The results showed that NGN, used singularly or in combination with radiation, can lower the procancerous and prometastatic Akt, p21, and MMP‑2 proteins while upregulating the apoptotic process.

Keywords: Akt; caspase‑3; matrix metalloproteinase‑2; non‑small cell lung cancer; naringenin; radiosensitization