Anticancer action of lactucopicrin in SKMEL-5 human skin cancer cells is mediated via apoptosis induction, G2/M cell cycle arrest and downregulation of m=TOR/PI3K/AKT signalling pathway

Abstract

Purpose: Skin cancer is one of the cancers responsible for significant morbidity and mortality across the globe. The treatment options for skin cancer are limited and associated with significant toxicity. Therefore, researches have been directed towards exploring molecules that could prove beneficial in the treatment of this disease. Lactucopicrin is an important sesquiterpene lactone with important pharmacological potential.

Methods: In the present study the anticancer effects of lactucopicrin against human skin SKMEL-5 cancer cell line were investigated. Antiproliferative effects were examined by CCK-8 assay. Apoptosis was detected by DAPI and annexin V/propidium iodide (PI) staining. Cell cycle analysis was carried out by flow cytometry. Protein expression was determined by western blotting.

Results: The results indicated that lactucopicrin exerts significant anticancer effects on the SKMEL-5 cells with an IC50 of 7.5 μM. Its anticancer effects were due to induction of apoptosis. Lactucopicrin could upregulate the expression of Bax which was associated with concomitant downregulation of Bcl-2 expression. Additionally, lactucopicrin induced G2/M cell cycle arrest in SKMEL-5 cells in a dose-dependent manner and also inhibited the m-TOR/PI3K/AKT signalling pathway.

Conclusion: These results indicate that lactucopicrin shows potent anticancer action in the tested skin cancer cells and may prove a prospective lead molecule for the treatment of skin cancer.