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TNFα induces Ca2+ influx to accelerate extrinsic apoptosis in hepatocellular carcinoma cells.


ABSTRACT: BACKGROUND:Tumor necrosis factor-α has been proven an effective anticancer agent in preclinical studies. However, the translation of TNFα from research to clinic has been blocked by significant systemic toxicity and limited efficacy at maximal tolerated dose, which need urgently to be solved. METHODS:The level of cytosolic Ca2+ was assessed by Fura-2 in HCC cells. After changing cytosolic Ca2+ level by using agonists or inhibitors, cell apoptosis was detected by flow cytometry. We also detected the effect of ionomycin or parvalbumin on the anti-tumor activity of TNFα in a mice model. Lastly, we studied the roles of cytosolic Ca2+ in the mitochondrial-dependent intrinsic apoptosis pathway. RESULTS:Here, we demonstrated that TNFα induced extracellular Ca2+ influx into cytoplasm through trans

SUBMITTER: Zhu J 

PROVIDER: S-EPMC5838867 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature