Targeted antitumor activity of Ginsenoside (Rg1) in paclitaxel-resistant human nasopharyngeal cancer cells are mediated through activation of autophagic cell death, cell apoptosis, endogenous ROS production, S phase cell cycle arrest and inhibition of m-TOR/PI3K/AKT signalling pathway.

PURPOSE

Nasopharyngeal carcinoma is one of common and vicious cancers of head and neck. The main purpose of this study was to examine the anticancer effects of the naturally occurring compound Ginsenoside (Rg1) against paclitaxel-resistant human nasopharyngeal cancer cells along with evaluation of its effects on cell autophagy, apoptosis, ROS production, cell cycle progression and m-TOR/PI3K/AKT signalling pathway.

METHODS

The viability of SUNE1 cancer cell line and NP460 normal cell line was checked by CCK8 counting assay. Apoptosis-related studies were examined by fluorescent microscopy using acridine orange (AO)/ethidium bromide (EB) staining as well as flow cytometry using annexin V assay. Further, transmission electron microscopy (TEM) was used to study autophagic effects induced by Ginsenoside (Rg1). Western blot assay was used to study the effects of Ginsenoside on apoptosis and on autophagy-related protein expressions including Bax, Bcl-2, LC3-ll.

RESULTS

The results indicated that Ginsenoside (Rg1) reduces the viability of the nasopharyngeal carcinoma cells in a dose-dependent manner, showing IC50 of 15 µM in cancer cells and IC50 of 80 µM in normal cell lines. The AO/EB staining showed that Ginsenoside (Rg1) inhibits the viability of cancer cells via induction of apoptotic cell death which was correlated with increase in Bax and decrease in Bcl-2 levels. Electron microscopic analysis showed that Ginsenoside (Rg1) caused the development of autophagosomes in cancer cells. Similarly, Ginsenoside (Rg1) increased the expression of LC3-II protein, indicating autophagic cell death. Ginsenoside (Rg1) also induced dose-dependent S phase cell cycle arrest. Western blot analysis showed that Ginsenoside (Rg1) has the potential to block m-TOR/PI3K/AKT signalling pathway.

CONCLUSIONS

In conclusion, the results of this study clearly indicate that Ginsenoside (Rg1) could be developed as a potent candidate drug against nasopharyngeal cancer provided further in vivo studies as well as toxicological studies are carried out.