Vitamin C Suppresses Pancreatic Carcinogenesis through the Inhibition of Both Glucose Metabolism and Wnt Signaling

Int J Mol Sci. 2022 Oct 14;23(20):12249. doi: 10.3390/ijms232012249.

Abstract

Cumulative studies have indicated that high-dose vitamin C has antitumor effects against a variety of cancers. However, the molecular mechanisms underlying these inhibitory effects against tumorigenesis and metastasis, particularly in relation to pancreatic cancer, are unclear. Here, we report that vitamin C at high concentrations impairs the growth and survival of pancreatic ductal adenocarcinoma (PDAC) cells by inhibiting glucose metabolism. Vitamin C was also found to trigger apoptosis in a caspase-independent manner. We further demonstrate that it suppresses the invasion and metastasis of PDAC cells by inhibiting the Wnt/β-catenin-mediated epithelial-mesenchymal transition (EMT). Taken together, our results suggest that vitamin C has therapeutic effects against pancreatic cancer.

Keywords: PDAC; Vitamin C; Wnt signaling; glucose metabolism; metastasis.

MeSH terms

  • Ascorbic Acid / pharmacology
  • Carcinogenesis
  • Carcinoma, Pancreatic Ductal* / pathology
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Epithelial-Mesenchymal Transition
  • Glucose / pharmacology
  • Humans
  • Pancreatic Neoplasms* / pathology
  • Wnt Signaling Pathway
  • beta Catenin / metabolism

Substances

  • beta Catenin
  • Ascorbic Acid
  • Caspases
  • Glucose

Grants and funding

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT & Future Planning (NRF-2019R1A2C4069947 to J.S.) and (NRF-2020R1C1C1012303), and by the National Research Foundation of Korea (NRF) MRC grant funded by the Korean government (MSIT) (2018R1A5A2020732).