Differential Response of Human Amniotic Membrane Proteins in Hepatocellular Carcinoma: Analysis of the Glycolytic Metabolism
Abstract Background: The human Amniotic Membrane (hAM) has been studied as a potential therapeutic option in cancer, namely in hepatocellular carcinoma. Previously, our research group evaluated the effect of human Amniotic Membrane Protein Extracts (hAMPE) in cancer therapy, demonstrating that hAMPE inhibit the metabolic activity of human hepatocellular carcinoma cell lines: Hep3B2.1-7, HepG2 and Huh7. Therefore, the aim of this study was to evaluate the effect of hAMPE treatment in glucose metabolism of hepatocellular carcinoma. Methods and Results: Glucose uptake and lactate production was assessed by 1H-NMR, and the expression of several mediators of the glycolytic pathway was evaluated by Western blot or fluorescence. Our results showed that hAMPE treatment increased glucose consumption on Hep3B2.1-7, HepG2, and Huh7 through the increase of GLUT1 in Hep3B2.1-7 and Huh7, and GLUT3 in HepG2 cells. It was observed increased expression of 6-phosphofrutokinase (PFK-1L) in all cell lines, indicating that glucose can be converted to pyruvate. Also, it was verified that glucose seems not to be converted to lactate on HepG2 and Huh7 cells, suggesting that hAMPE treatment may contradict the Warburg effect observed in carcinogenesis. In Hep3B2.1-7, the hAMPE treatment induced an increase in expression of lactate dehydrogenase (LDH) and monocarboxylate transporter isoform 4 (MCT4). Conclusions: Overall, this work highlighted the potential usefulness of hAMPE as anticancer therapy through the modulation of the glycolytic metabolism in human hepatocellular carcinoma.