Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Gossypol Induces Apoptosis of Human Pancreatic Cancer Cells via CHOP/Endoplasmic Reticulum Stress Signaling Pathway

  • Lee, Soon (Division of Analytical Science, Korea Basic Science Institute) ;
  • Hong, Eunmi (Division of Analytical Science, Korea Basic Science Institute) ;
  • Jo, Eunbi (Department of Life Science and Research Institute for Natural Sciences, College of Natural Sciences, Hanyang University) ;
  • Kim, Z-Hun (Microbial Research Department, Nakdonggang National Institute of Biological Resources) ;
  • Yim, Kyung June (Microbial Research Department, Nakdonggang National Institute of Biological Resources) ;
  • Woo, Sung Hwan (Department of Biological Engineering, Inha University) ;
  • Choi, Yong-Soo (Department of Biotechnology, CHA University) ;
  • Jang, Hyun-Jin (Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology)
  • Received : 2021.10.13
  • Accepted : 2022.02.21
  • Published : 2022.05.28
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Abstract

Gossypol, a natural phenolic aldehyde present in cotton plants, was originally used as a means of contraception, but is currently being studied for its anti-proliferative and anti-metastatic effects on various cancers. However, the intracellular mechanism of action regarding the effects of gossypol on pancreatic cancer cells remains unclear. Here, we investigated the anti-cancer effects of gossypol on human pancreatic cancer cells (BxPC-3 and MIA PaCa-2). Cell counting kit-8 assays, annexin V/propidium iodide staining assays, and transmission electron microscopy showed that gossypol induced apoptotic cell death and apoptotic body formation in both cell lines. RNA sequencing analysis also showed that gossypol increased the mRNA levels of CCAAT/enhancer-binding protein homologous protein (CHOP) and activating transcription factor 3 (ATF3) in pancreatic cancer cell lines. In addition, gossypol facilitated the cleavage of caspase-3 via protein kinase RNA-like ER kinase (PERK), CHOP, and Bax/Bcl-2 upregulation in both cells, whereas the upregulation of ATF was limited to BxPC-3 cells. Finally, a three-dimensional culture experiment confirmed the successful suppression of cancer cell spheroids via gossypol treatment. Taken together, our data suggest that gossypol may trigger apoptosis in pancreatic cancer cells via the PERK-CHOP signaling pathway. These findings propose a promising therapeutic approach to pancreatic cancer treatment using gossypol.

Keywords

Acknowledgement

This study was supported by a grant (Project No. NNIBR202202109) from Nakdonggang National Institute of Biological Resources funded by the Ministry of Environment of the Korean government.

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