Abstract
Litchi chinensis Sonnerat is a tropical tree whose fruits contain significant amounts of bioactive polyphenols. Litchi cultivation has recently spread in Sicily where the climate conditions are particularly favorable for this crop. Recent findings have shown that Litchi extracts display anti-tumor and pro-apoptotic effects in vitro, but the precise underlying mechanisms have not been fully elucidated. In this study, we report for the first time the effects of Sicilian litchi fruit extracts on colon cancer cells. The results indicated that litchi exocarp, mesocarp and endocarp fractions reduce the viability and clonogenic growth of HT29 cells. These effects were due to cell cycle arrest in the G2/M phase followed by caspase-dependent cell death. Interestingly, litchi exocarp and endocarp triggered a precocious autophagic response (16–24 h), which was accompanied by an increase in the level of autophagy related 1/autophagy activating kinase 1 (ATG1/ULK1), beclin-1, microtubule associated protein 1 light chain 3 (LC3)-II and p62 proteins. Autophagy inhibition by bafilomycin A1 or beclin-1 silencing increased cell death, thus suggesting that autophagy was initially triggered as a pro-survival response. Significant effects of Litchi extracts were also observed in other colon cancer cells, including HCT116 and Caco-2 cells. On the other hand, differentiated Caco-2 cells, a model of human enterocytes, appeared to be insensitive to the extracts at the same treatment conditions. High-Performance Liquid Chromatography–Electrospray Ionization-Quadrupole-Time-Of-Flight HPLC/ESI/Q-TOF evidenced the presence of some polyphenolic compounds, specifically in exocarp and endocarp extracts, that can account for the observed biological effects. The results obtained suggest a potential therapeutic efficacy of polyphenolic compounds purified from Sicilian Litchi fractions for the treatment of colon cancer. Moreover, our findings indicate that modulation of autophagy can represent a tool to improve the effectiveness of these agents and potentiate the anti-tumor response of colon cancer cells.
Highlights
Litchi chinensis Sonnerat is a fruit tree belonging to the Sapindaceae family, originally cultivated inChina and subsequently spread to tropical and sub-tropical areas worldwide [1,2,3]
In the first phase of this study, we evaluated the amount of polyphenols in Sicilian litchi fruit significant at a p value < 0.05
(16–24 h)vacuoles with litchi extracts upper panel), which are not evident in the presence of litchi mesocarp. In light of this observation, we indicated that the exocarp and endocarp provoke the appearance of big cytoplasmic vacuoles (Figure 3a, speculated that which litchi exocarp and endocarp induction apoptosis, could upper panel), are not evident in the extracts, presence besides of litchithe mesocarp
Summary
Litchi chinensis Sonnerat is a fruit tree belonging to the Sapindaceae family, originally cultivated inChina and subsequently spread to tropical and sub-tropical areas worldwide [1,2,3]. Litchi chinensis Sonnerat is a fruit tree belonging to the Sapindaceae family, originally cultivated in. Recent studies have shown that litchi pulp (mesocarp) contains bioactive compounds, including polysaccharides with strong antioxidant activities [6,7]. Have provided evidence that litchi pulp displays anti-tumor and immunomodulatory effects both in vitro and in vivo [8]. Hsu et al have shown that litchi seed extract exerts anti-tumor and pro-apoptotic actions in human colorectal carcinoma cells [9]. Litchi peel (exocarp) has been shown to contain active flavonoids and anthocyanins which display anti-oxidant properties and can exert anti-cancer effects [10]. The anti-tumor action of litchi exocarp was found in human breast cancer cells as well as breast cancer mouse xenografts [11]
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