The Mechanism of Lethal Effect of High-dose Vitamin C on Renal Cancer Cells
|Tutor||Migue lA. Esteban|
|School||University of Science and Technology of China|
|Course||Biochemistry and Molecular Biology|
|Keywords||Cancer Hypoxia-inducible factor Vitamin C ATP dips Warburg effect Necrosis|
The role of vitamin C in cancer treatment has been studied for decades , clinical studies have shown that high concentrations of intravenous vitamin C can have a positive effect on cancer treatment , and in vitro experiments showed that cancer cells than in normal cells easier vitamin C to kill However , the mechanism of cytotoxicity of the vitamin C, as well as selective cytotoxic effect remains unknown . Kidney transparent type of renal carcinoma (CCRCC) as the tumor cell research models , the cytotoxic mechanism of kidney cancer by studying vitamin C , found that vitamin C can be dependent on hypoxia-inducible factor (HIF) -mediated cell death , in order to this is the entry point for our progress , the expression of HIF -positive renal carcinoma cells by tumor cells generally have higher expression of GLUT1 in intracellular accumulation of vitamin C , and with intracellular iron ion reaction to produce more reactive oxygen ( ROS), to induce severe DNA damage . In addition, the cells to repair DNA damage will cause the sudden drop in NAD and ATP by -Warburg effect ‖ due to HIF -positive kidney cancer cells obtain energy inefficient glycolytic pathway , NAD and ATP plunged buffering capacity than weak cells therefore toward necrosis . Our studies to clarify the mechanism of vitamin C on renal carcinoma cell cytotoxicity and its selective cytotoxic effect produced , and provide a good model for multi-target compound screening drugs against tumor characteristics .