Mychonastes sp. 246 Suppresses Human Pancreatic Cancer Cell Growth via IGFBP3-PI3K-mTOR Signaling

• Published in: Journal of microbiology and biotechnology Vol. 33; no. 4; pp. 449 - 462
• Main Authors: Jang, Hyun-Jin, Lee, Soon, Hong, Eunmi, Yim, Kyung June, Choi, Yong-Soo, Jung, Ji Young, Kim, Z-Hun
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Society for Microbiology and Biotechnology 28-04-2023
• Subjects: Apoptosis; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation; Humans; Insulin-Like Growth Factor Binding Protein 3 - metabolism; Insulin-Like Growth Factor Binding Protein 3 - pharmacology; Pancreatic Neoplasms; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - metabolism; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Research article; Signal Transduction; TOR Serine-Threonine Kinases - metabolism; TOR Serine-Threonine Kinases - pharmacology; IGFBP; mTOR; pancreatic cancer; PI3K; cell cycle arrest; Mychonastes sp
• ISSN: 1017-7825; 1738-8872
• DOI: 10.4014/jmb.2211.11010

Previously, we confirmed that
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.