The Antitumor Mechanism Of PAHDAA In Colon Carcinoma Cells

BackgroundIn recent years,the incidence and mortality of colorectal cancer in China are high in malignant tumors.Cancer data released by the China Cancer data Center in 2019 show that the incidence of colorectal cancer has risen to the third place,the mortality rate is still in the fifth place,so the burden of colorectal cancer is still huge,and most of the findings are already in the middle and late stages of surgery,the surgical results are poor.With the study of dithiocarbamate and its derivatives,the anti-cancer effect of dithiocarbamate is a new hope for more cancer patients.The antitumor mechanism of PAHDAA on colon cancer cells was studied in this paper.ObjectiveTo investigate the anti-tumor mechanism of pyridinaldehyde Hydrazone dithiocarb-amate acetic acid?PAHDAA?on colon cancer cells.Methods1.The inhibitory effect of PAHDAA on the growth of human colon cancer cell line HCT116 was detected by succinate dehydrogenase activity assay?MTT?.2.Flow cytometry was used to determine the ability of PAHDAA to produce ROS in cells.3.The effects of PAHDAA on cell growth inhibition were detected by RT-PCR and Western Blot,respectively.4.The effects of different concentrations of PAHDAA on human colon cancer cell line HCT-116 were observed by Acridine orange staining.5.Lyso-tracker red staining confirmed that PAHDAA induced lysosome membrane permeability change by ferritin autophagy.Results1.PAHDAA inhibited the growth of human colon cancer cell line HCT116(IC₅₀=9.29±0.021?mol/l).2.PAHDAA can increase the formation of intracellular free radical?ROS?.3.The results of RT-PCR and Western Blot showed that the down regulation of PAHDAA through FTH1 and the upregulation of NCOA4 suggested the existence of ferritin autophagy.4.Acridine orange staining confirmed that PAHDAA could accelerate the apoptosis of human colon cancer cell line HCT116 by ferritin autophagy,and the anticancer effect increased with the increase of concentration.5.Lyso-Tracker Red staining showed that PAHDAA induced lysosome membrane permeability change through ferritin autophagy,and then affected cell apoptosis.With the increase of concentration,the faster the apoptosis rate was.ConclusionsPAHDAA plays an anti-tumor effect on colon cancer cells by inducing ferritin autophagy.