Alantolactone exhibits selective antitumor effects in HELA human cervical cancer cells by inhibiting cell migration and invasion, G2/M cell cycle arrest, mitochondrial mediated apoptosis and targeting Nf-kB signalling pathway.

PURPOSE

Cervical cancer is responsible for significant mortality and morbidity across the globe. Owing to the adverse effects of the currently used chemotherapy, research is directed to develop effective and safer chemotherapy for cervical cancer. This study was therefore designed to examine the effects of Alantolactone (AL) against a panel of human cervical cancer cells (HeLa, C4-1, MEK-180, C33A) and a normal cell line (HCerEPiC).

METHODS

Cell viability was examined by WST-1 assay. Cell migration and invasion were examined by transwell assay. Cell cycle analysis was performed by flow cytometry. Apoptosis was detected by annexin V/propidium iodide (PI) and DAPI staining. Western blot analysis was used to examine protein expression.

RESULTS

The results revealed that AL inhibits the growth of the all the cervical cancer cells in a concentration -dependent manner and exhibited the lowest IC50 of 15 µM against the HeLa cervical cancer cells. The anticancer effects of AL were due to induction of mitochondrial mediated apoptosis. AL caused enhancement in the expression of apoptosis regulatory proteins such as caspase 3 and Bax in cervical cancer cells. AL not only prompted the accumulation of the cervical cancer cells in the G2/M phase of the cell cycle but also inhibited the expressions of various cyclins. Transwell assay revealed that AL suppresses the migration and invasion of cervical cancer cells. Moreover AL could also block the NF-kB signalling pathway concentration-dependently.

CONCLUSIONS

It is concluded that AL may serve as an important lead molecule for the development of therapy for cervical cancer.