In vitro and in vivo cytotoxic effects of chrysoeriol in human lung carcinoma are facilitated through activation of autophagy, sub-G1/G0 cell cycle arrest, cell migration and invasion inhibition and modulation of MAPK/ERK signalling pathway.

PURPOSE: Lung cancer is a malignancy that imposes huge health, psychological and financial burden on patients and their families. Owing to lack of viable treatment options and late diagnosis, there is need for the development of new candidate drugs. In the current study the anticancer potential of Chrysoeriol was examined against lung cancer cells.
METHODS: The proliferation rate of the lung cancer cells was checked by WST-1 assay. Autophagy was detected by electron microscopy and propidium iodide (PI) staining. Cell cycle analysis was performed by flow cytometry. Protein expression was determined by immuno blotting. Xenografted mice models were used for in vivo evaluation of Chrysoeriol.
RESULTS: The results revealed that Chrysoeriol could significantly inhibit the proliferation of the A549 lung cancer cells with lower cytotoxicity against the normal MRC-5 cells. The anticancer activity of Chrysoeriol against the A549 cells was due to induction of autophagy. The Chrysoeriol-prompted autophagy was also associated with alteration in the autophagy-related protein expression. The expression of LC3II and Beclin-1 was significantly upregulated upon chrysoeriol treatment. Chrysoeriol could also induce sub-G1/G0 cell cycle arrest. Furthermore, it could also inhibit the migration and invasion of the A549 cells. In addition, it was observed that Chrysoeriol could inhibit the MAPK/ERK signalling pathway in the A549 lung cancer cells. The effects of the Chrysoeriol were also examined in vivo in xenografted mice models which revealed that Chrysoeriol inhibited the growth of xenografted tumors.
CONCLUSIONS: Chrysoeriol considerably and selectively suppresses the growth of lung cancer in vitro and in vivo and may prove beneficial in the management of this disease.