Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Mychonastes sp. 246 Suppresses Human Pancreatic Cancer Cell Growth via IGFBP3-PI3K-mTOR Signaling

  • Hyun-Jin Jang (Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology) ;
  • Soon Lee (Division of Analytical Science, Korea Basic Science Institute) ;
  • Eunmi Hong (Division of Analytical Science, Korea Basic Science Institute) ;
  • Kyung June Yim (Microbial Research Department, Nakdonggang National Institute of Biological Resources) ;
  • Yong-Soo Choi (Department of Biotechnology, CHA University) ;
  • Ji Young Jung (Microbial Research Department, Nakdonggang National Institute of Biological Resources) ;
  • Z-Hun Kim (Microbial Research Department, Nakdonggang National Institute of Biological Resources)
  • Received : 2022.11.07
  • Accepted : 2022.11.28
  • Published : 2023.04.28
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Abstract

Previously, we confirmed that Mychonastes sp. 246 methanolic extract (ME) markedly reduced the viability of BxPC-3 human pancreatic cancer cells. However, the underlying mechanism ME remained unclear. Hence, we attempted to elucidate the anticancer effect of ME on BxPC-3 human pancreatic cancer cells. First, we investigated the components of ME and their cytotoxicity in normal cells. Then, we confirmed the G1 phase arrest mediated growth inhibitory effect of ME using a cell counting assay and cell cycle analysis. Moreover, we found that the migration-inhibitory effect of ME using a Transwell migration assay. Through RNA sequencing, Gene Ontology-based network analysis, and western blotting, we explored the intracellular mechanisms of ME in BxPC-3 cells. ME modulated the intracellular energy metabolism-related pathway by altering the mRNA levels of IGFBP3 and PPARGC1A in BxPC-3 cells and reduced PI3K and mTOR phosphorylation by upregulating IGFBP3 and 4E-BP1 expression. Finally, we verified that ME reduced the growth of three-dimensional (3D) pancreatic cancer spheroids. Our study demonstrates that ME suppresses pancreatic cancer proliferation through the IGFBP3-PI3K-mTOR signaling pathway. This is the first study on the anticancer effect of the ME against pancreatic cancer, suggesting therapeutic possibilities and the underlying mechanism of ME action.

Keywords

Acknowledgement

This study was supported by a grant (Project No. NNIBR202303101) from Nakdonggang National Institute of Biological Resources funded by the Ministry of Environment of the Korean government.

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