Fig. 7: Tan IIA increases the sensitivity of heat-induced Huh-7 cells to hyperosmotic stress and inhibits glycolysis by deactivating ALDH7A1. | Cell Death Discovery

Fig. 7: Tan IIA increases the sensitivity of heat-induced Huh-7 cells to hyperosmotic stress and inhibits glycolysis by deactivating ALDH7A1.

From: Tanshinone IIA inhibits heat-induced growth of p53-mutant Huh-7 hepatocellular carcinoma by modulating osmotic homeostasis and glycolysis through targeting ALDH7A1

Fig. 7

Visualization of the molecular docking between Tan IIA and ALDH7A1 protein using PyMOL 2.3.0 (A) and LigPlot v2.2.8 (B). C, D The direct interaction between ALDH7A1 and Tan IIA or 4-diethylaminobenzaldehyde (DEAB, positive control) tested using cellular thermal shift assay (CETSA). **p < 0.01, vs 0 μg/mL. Viability (E) and apoptosis (F, G) of heat-induced Huh-7 cells, respectively, treated with shALDH7A1 lentivirus, DEAB, and Tan IIA for 48 h. H–J Comparison of gene expression of heat-induced Huh-7 cells, respectively, treated with shALDH7A1, DEAB, and Tan IIA, and the intersection of the corresponding GO or KEGG pathway enrichment results: DEG expression profile (H), Venn diagrams of GO (I) or KEGG pathway (J) terms. **p < 0.01, compared with Blank; # p < 0.05, compared with shNC; + p < 0.05, compared with shALDH7A1. K–M The anti-viability and proapoptotic effects of Tan IIA on the cells with scarce ALDH7A1 are attenuated. **p < 0.01, compared with shNC in Iso or Hyper group; # p < 0.05, compared with shNC+Tan IIA. N–P NaCl-mediated hyperosmotic stress inhibits viability and induces apoptosis, and Tan IIA further inhibits viability of heat-induced Huh-7 cells with or without ALDH7A1 OE in the presence of NaCl-mediated hyperosmotic stress. Q, R Hyperosmotic stress increases glucose uptake and ATP production, and Tan IIA reduces them in heat-induced Huh-7 cells with or without ALDH7A1 OE in the presence of hyperosmotic stress. S Tan IIA promotes lactate production in heat-induced Huh-7 cells overexpressing ALDH7A1 in the presence of hyperosmotic stress, and heat-induced cells overexpressing ALDH7A1 produces more lactate after Tan IIA treatment in hyperosmotic culture media. T, U Hyperosmotic stress induces betaine and d-glycerate, which can be enhanced by ALDH7A1 OE, and Tan IIA blocks the induction. S Hyperosmotic stress increases ROS level in heat-induced cells, and Tan IIA causes excessive ROS. For (N–V), ** p < 0.01, compared with EV+Iso; # p < 0.05, ## p < 0.01, compared with EV+Hyper; + p < 0.05, compared with ALDH7A1-OE+Hyper; NS not significant.

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