ABSTRACT
This study aimed at exploring the effects of Griffipavixanthone,a natural small molecule extracted from Garcinia esculenta,on the autophagy and the mechanism behind it.Cervical cancer HeLa cells were selected as the model in vitro.Confocal microscopy,flow cytometry and immunoblotting were performed to know the impacts of Griffipavixanthone on signaling pathway over autophagy flux and calcium level;while nude mouse model was established to explore its anti-cancer action in vivo.It was found that Griffipavixanthone significantly induced GFP-LC3 puncta formation and the accumulation of LC3-Ⅱ/LC3-Ⅰ,and increased the protein expression of SQSTM1 in HeLa cells in a time and concentration dependent manner.MTT assay results showed that Griffipavixanthone inhibited the growth of HeLa cells in a dosage dependent manner,and eliminated the tolerance of tumor cells to nutrient starvation,which fastened the death of cells.Griffipavixanthone also down-regulated the concentration of calcium in the cytoplasm.Furthermore,the in vivo study indicated that intratumoral injection of Griffipavixanthone presented the anti-cancer effect to a certain extent.In conclusion,it was suggested that Griffipavixanthone inhibit autophagy with the potential to be developed into a clinical anti-cancer agent.Griffipavixanthone sensitized HeLa cells to nutrient stress-induced cell death through inhibiting the autophagy flux and the level of calcium in the cytoplasm.