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. 2021 Dec 16;118(51):e2107220118. doi: 10.1073/pnas.2107220118

Fig. 3.

Fig. 3.

Tri-CAP treatment induces a widespread blockade of cancer survival pathways, including deregulated redox balance, glycolysis, and proliferative signaling in BCR-ABL1+ cells, while having little impact on parental cells. Tri-CAP treatment for 60 s induces a significant elevation of diverse intracellular ROS (n = 3) (A), sustained reduction of the GSH to GSSG ratio (B), and total antioxidant capacity (n = 4) (C), preferentially leading to excessive oxidative stress and reduced antioxidant defense in resistant BCR-ABL1T315I cells relative to parental cells (D). (E) Tri-CAP treatment further reduces protein expression levels of six glycolytic enzymes, as evident from quantification of band intensities shown at right (n = 3). (F) These effects are predicted to disrupt glycolysis at multiple enzymatic points, thereby impeding cross-talk for supporting the maintenance of redox balance in resistant BCR-ABL1T315I cells. Tri-CAP preferentially reduces protein expression of HIF-1α and blocks phosphorylation of mTOR and AKT at 6-h posttreatment in BCR-ABL1+ cells (n = 3) (G), thus facilitating attenuation of the AKT/mTOR/HIF-1α signaling pathway at multiple nodes (H). *P < 0.05, **P < 0.01, and ***P < 0.001. TCA, tricarboxylic acid.