Anticancer properties of dried-pericarp water extracts of Camellia japonica L. fermented with Aspergillus oryzae through regulation of IGFBP-2/mTOR pathway

Sci Rep. 2021 Nov 2;11(1):21527. doi: 10.1038/s41598-021-01127-3.

Abstract

This study aimed to investigate the anticancer activity of dried-pericarp water extract of fermented C. japonicus (CJ). The dried-pericarp water extracts of CJ were fermented using Aspergillus oryzae and Saccharomyces cerevisiae at 30 °C and 35 °C. The anticancer activities of both water extracts fermented at 30 °C and 35 °C using A. oryzae against FaDu cells were remarkably changed compared with unfermented dried-pericarp water extract of CJ, which has no anticancer activity. Cleaved-PARP, caspase 3, and apoptotic cells stained with annexin V/PI were significantly increased by treatment with A. oryzae extracts fermented at 30 °C. The insulin-like growth factor-binding protein 2 (IGFBP-2) protein level and mTOR phosphorylation by A. oryzae fermented extracts (AOFE) were dramatically reduced, and the expression levels of IGFBP-2 and phosphorylated mTOR were significantly increased depending on the glucose concentrations in FaDu cells. These results suggested that the cell viabilities in AOFE were restored as the glucose concentrations increased. Furthermore, it was confirmed LC/MS/MS that the content of gallic acid was increased by fermentation of Aspergillus oryzae (5.596 ± 0.1746 μg/mg) compared to the unfermented extract (1.620 ± 0.0432 μg/mg). Based on these results, the anticancer effect of AOFE was achieved through inhibition of the IGFBP-2/mTOR signaling pathway. These results suggest that AOFE may be a potential treatment for head and neck cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Aspergillus oryzae / chemistry*
  • Camellia / chemistry*
  • Fermentation
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / pathology
  • Humans
  • Insulin-Like Growth Factor Binding Protein 2 / genetics
  • Insulin-Like Growth Factor Binding Protein 2 / metabolism*
  • Plant Extracts / pharmacology*
  • Squamous Cell Carcinoma of Head and Neck / drug therapy
  • Squamous Cell Carcinoma of Head and Neck / metabolism
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism*
  • Tumor Cells, Cultured
  • Water / chemistry

Substances

  • Antineoplastic Agents
  • Insulin-Like Growth Factor Binding Protein 2
  • Plant Extracts
  • Water
  • TOR Serine-Threonine Kinases