Inhibition of nasopharyngeal cells mediated via G2/M cell cycle arrest, blocking PI3K/AKT/mTOR signalling pathway and suppression of cell migration and invasion

Abstract

Nasopharyngeal carcinoma (NPC) is a less common but destructive cancer. Because of distant metastasis and deleterious side effects, there is persistent need to identify effective treatment options for nasopharyngeal cancer. In the current research work, the anticancer effects of Abietic acid were evaluated against the cisplatin resistant nasopharyngeal cancer cells. MTT (3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide) assay was executed for monitoring cell proliferation rate. Annexin V/propidium iodide and acridine orange/ethidium bromide assays were executed to investigate effects on cell apoptosis. Flow cytometry was employed to observe the effects on different phases of cell cycle. Cancer Cell migration and cell invasion was checked by transwell assays. Western blotting was done to evaluate impact on protein expression. It was found that Abietic acid exerts potent antiproliferative against the nasopharyngeal cancerous cell line and exhibited an IC50 of 20 μM. However the toxic effects of abietic acid in comparison to cancerous cells were seen to be insignificant against the normal cells. The antitumor impact of abietic acid was exerted through apoptosis induction and alteration of apoptosis related proteins (Bax, caspase 3 and 9). Abietic acid also caused (ROS) reactive oxygen species arbitrated changes in the MMP (mitochondrial transmembrane potential) and triggered cell cycle arrest at G2/M phase. Finally, Abietic acid could also inhibit the invasiveness of cancer cells and migration of the NPC cells. Abietic acid could also block the PI3K/AKT/mTOR biochemical signalling cascade in the HNE1 cells which remains a significant therapeutic objective of anticancer drugs. In conclusion, the results indicate that abietic acid might be a promising drug candidate and promising treatment option for nasopharyngeal carcinoma.