Artemisia Umbelliformis SSP. Eriantha extract inhibits hepatocarcinoma cell growth and invasion

Objective: Hepatocellular carcinoma (HCC) is the most frequent primary malignant disease of the liver and the second leading cause of cancer related mortality in the world. Discovering new compounds able to improve patient survival, alone or in combination, represents a priority. Artemisia annua L., a plant acknowledged for its antimalarial effects, also shows important anticancer activities towards several kinds of tumors, including hepatocarcinoma. The aim of this study was to verify the antitumoral potential of other plants of Artemisia genus, such as the Central Apennine subendemic species A. umbelliformis ssp. eriantha (Ten.) Vallès-Xirau & Oliva Brañas. Methods: Two hepatocarcinoma cell lines, HepG2 and Huh7, and a differentiated hepatocyte line, HepaRG, were used. Following treatment with alcoholic extracts of the aerial parts of the plant, cell proliferation was evaluated by neutral red assay, cell cycle and apoptosis by flow cytometry, cell migration by wound healing assay, and expression of cell cycle and apoptosis molecules by Western blotting. Results: Treatment reduced cell growth of both HepG2 and Huh7 cells, with no effect on the differentiated HepaRG cells. In addition, Huh7 cells also exhibited lower healing after scratch wound, increased apoptotic cell fraction and elevated p21, p27 and p53 expression. Conclusions: A.umbelliformis ssp. eriantha extract interferes with key factors of hepatocyte proliferation and invasion and emerges as a promising adjuvant for prevention and/or treatment of hepatocellular carcinoma.