Autophagic cell death induced by Litchi fruit extracts in human colon cancer cells

Litchi chinensis is a tropical fruit which cultivation has been recently introduced in Sicily. Some findings have shown that Litchi extracts display antitumor effects but the underlying mechanisms have not been elucidated. This study focuses on the effects of Litchi hydro-alcoholic extracts in colorectal cancer cells. The results indicated that Litchi exocarp (peel), mesocarp (pulp) and endocarp (seeds) extracts reduce the viability of HT-29 colon cancer cells in a dose dependent manner. This effect was accompanied with G2/M arrest of the cell cycle followed by cell death. Interestingly, exocarp and endocarp extracts triggered an autophagic response in the first phase of treatment (16-24h) with increase in the protein levels of ATG1/ Ulk kinase, p62 and LC3-II accumulation. In particular, time point evaluation indicated that with exocarp extracts the autophagic form LC3II appeared at 16h treatment whereas with endocarp extracts accumulated at 48h. ATG1/Ulk and p62 increased early at 16 h treatment in both cases and p62 remained elevated until 48h. On the other hand, autophagic effects were not observed with Litchi mesocarp extracts which directly induced caspase 3-dependent apoptosis. Polyphenol colorimetric assay showed that the Litchi extracts contain significant amounts of these compounds, particularly in exocarp and endocarp. Accordingly, treatment of cells with gallic acid, one bioactive component of polyphenols, mimicked the effects of the Litchi extracts. Taken together, these preliminary results provides in vitro evidence that litchi extracts activate the autophagic process preceding cell death and can thus be considered as potential chemopreventive agents for colorectal cancer.