(b) Western blotting of LC3, p62 and caspase-3 after treatment of HCT116 cells with litchi extracts (75 g/mL) for 16 h or 48 h. 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 Noradrenaline bitartrate monohydrate (Levophed) extracts at the same treatment conditions. High-Performance Liquid ChromatographyCElectrospray 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. is a fruit tree belonging to the Sapindaceae family, originally cultivated in China Noradrenaline bitartrate monohydrate (Levophed) and subsequently spread to tropical and sub-tropical areas worldwide [1,2,3]. Cultivation of the litchi tree has been recently launched in Sicily (Italy), where the climatic conditions are particularly favorable for planting and crop of tropical plants [4,5]. The fruit is known for its good taste and nutritional properties [3]. Recent studies have shown that litchi pulp (mesocarp) contains bioactive compounds, including polysaccharides with strong antioxidant activities [6,7]. In addition, Huang et al. have also provided evidence that litchi pulp displays anti-tumor and immunomodulatory effects Noradrenaline bitartrate monohydrate (Levophed) both in vitro and in vivo [8]. Other non-edible parts of the litchi fruit are also employed in popular Chinese medicine. Litchi seeds (endocarp) are used as analgesic to relieve gastralgia, cough and neuralgia [3]. Moreover, Hsu et al. have shown that litchi seed extract exerts anti-tumor and pro-apoptotic actions in human colorectal carcinoma cells [9]. However, the precise mechanism of action for apoptosis induction remains to be elucidated. 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]. Autophagy is Noradrenaline bitartrate monohydrate (Levophed) a highly conserved process that consists of the degradation of cellular components and nutrients to maintain cell homeostasis and survival during stress conditions. It can result in either cell survival or cell death depending on various circumstances [12]. The autophagic process is highly regulated by autophagy related gene products, named autophagy related (ATG) proteins. In the first phase of autophagy, a central component is Unc-51 like autophagy activating kinase (ULK1), a kinase encoded by the gene, which triggers the recruitment of other ATG proteins, including beclin-1, a component of the class III PI-3K complex, and ATG12 and ATG5 to form the phagophore [13]. Concomitantly, a cytosolic form of the microtubule associated protein 1 light chain 3 (LC3) protein (LC3-I) forms the LC3-phosphatidylethanolamine conjugate (LC3-II), which is recruited to autophagosomal membranes and therefore acts as a process marker [14,15]. In cancer cells, autophagy plays an important role as a tumor promoter or exerting tumor suppressor functions [16,17]. Tumor cells can indeed activate a pro-survival autophagic process in starvation or hypoxic conditions and increase growth and aggressiveness [18]. On the other hand, several studies suggest that autophagy can prevent tumor initiation [19]. Moreover, the induction of autophagic cell death can represent a tool for targeting tumor cells, particularly when resistance to classic apoptosis occurs. Autophagy can thus provide a useful method to limit tumor progression Rabbit polyclonal to AK3L1 and enhance the efficacy of anti-cancer treatments. However, in many cases, triggering autophagic flux may represent a defensive cell mechanism against cytotoxic treatments and thus inhibiting the process may result in potentiating cell death [20]. As it is known that climatic conditions can influence the chemical composition of Noradrenaline bitartrate monohydrate (Levophed) the fruit, we aimed to investigate the cytotoxic effects of litchi cultivated in Sicily. In this paper, we provide.