The electrochemical behavior of copper(II) or zinc(II) metal ions was investigated in the presence of different pH buffers [3‐(N‐morpholino)‐2‐hydroxypropanesulfonic acid (MOPSO), 2‐(N‐morpholino)ethanesulfonic acid (MES) and 3‐(N‐morpholino)propanesulfonic acid (MOPS)] by differential pulse anodic stripping voltammetry (DPASV) and differential pulse polarography (DPP). These studies showed that these pH buffers did not complex zinc or copper, but MOPSO and MOPS modified the reversibility of copper electrochemical DPASV and DPP (only MOPSO) responses, under the experimental conditions used. Depression of peak current for both metal ions was also observed in the presence of all pH buffers due to surface coverage of the electrode by those compounds, which was verified by alternating current voltammetry (ACV).
Metabolic reprogramming is a central hub in tumor development and progression. Therefore, several efforts have been developed to find improved therapeutic approaches targeting cancer cell metabolism. Recently, we identified the 7α-acetoxy-6β-benzoyloxy-12-O-benzoylroyleanone (Roy-Bz) as a PKCδ-selective activator with potent anti-proliferative activity in colon cancer by stimulating a PKCδ-dependent mitochondrial apoptotic pathway. Herein, we investigated whether the antitumor activity of Roy-Bz, in colon cancer, could be related to glucose metabolism interference. The results showed that Roy-Bz decreased the mitochondrial respiration in human colon HCT116 cancer cells, by reducing electron transfer chain complexes I/III. Consistently, this effect was associated with downregulation of the mitochondrial markers cytochrome c oxidase subunit 4 (COX4), voltage-dependent anion channel (VDAC) and mitochondrial import receptor subunit TOM20 homolog (TOM20), and upregulation of synthesis of cytochrome c oxidase 2 (SCO2). Roy-Bz also dropped glycolysis, decreasing the expression of critical glycolytic markers directly implicated in glucose metabolism such as glucose transporter 1 (GLUT1), hexokinase 2 (HK2) and monocarboxylate transporter 4 (MCT4), and increasing TP53-induced glycolysis and apoptosis regulator (TIGAR) protein levels. These results were further corroborated in tumor xenografts of colon cancer. Altogether, using a PKCδ-selective activator, this work evidenced a potential dual role of PKCδ in tumor cell metabolism, resulting from the inhibition of both mitochondrial respiration and glycolysis. Additionally, it reinforces the antitumor therapeutic potential of Roy-Bz in colon cancer by targeting glucose metabolism.
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