Figure 8 | Scientific Reports

Figure 8

From: Low-dose YC-1 combined with glucose and insulin selectively induces apoptosis in hypoxic gastric carcinoma cells by inhibiting anaerobic glycolysis

Figure 8

In vitro apoptotic effect of low-dose YC-1 + GI treatment on hypoxic 58As9 cells. (a) HIF-1α controls ROS production in hypoxic 58As9 cells by up-regulating genes involved in anaerobic glycolysis such as GLUT1, ALDOC, LDHA, PDK1 and MCT4 (indicated by red letters). (b) Low-dose YC-1 + GI treatment induces hypoxia-dependent apoptosis in 58As9 cells. YC-1 treatment inhibits HIF-1α expression in hypoxic 58As9 cells and suppresses up-regulation of the HIF-1α targets GLUT1, ALDOC, PDK1 and MCT4 (indicated by gray letters). Attenuation of the expression of these genes causes a metabolic switch from anaerobic glycolysis to OXPHOS in hypoxic 58As9 cells, resulting in the elevated OCR/ECAR ratio. Additionally, GI treatment accelerates GLUT1 membrane translocation (indicated by red letters) via insulin signalling, promotes glucose uptake in hypoxic 58As9 cells, and contributes to increased AcCoA entry into the TCA cycle. These dual effects of low-dose YC-1 + GI treatment result in lethal ROS production through the ETC. CM: cell membrane, NC: nucleus, HRE: hypoxia responsive element, MC: mitochondria, GL: glycolysis, IR: insulin receptor. AcCoA: acetyl-CoA, OCR: oxygen consumption rate, ECAR: extracellular acidification rate.

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