Chelidonine Induces Apoptosis via GADD45a-p53 Regulation in Human Pancreatic Cancer Cells

Integr Cancer Ther. 2021 Jan-Dec:20:15347354211006191. doi: 10.1177/15347354211006191.

Abstract

Chelidonium majus has been used as a traditional medicine in China and western countries for various diseases, including inflammation and cancer. However, the anti-cancer effect of chelidonine, a major compound of C. majus extracts, on pancreatic cancer remains poorly understood. In this study, we found that treatment with chelidonine inhibited proliferation of BxPC-3 and MIA PaCa-2 human pancreatic cancer cells. Annexin-V/propidium iodide staining assay showed that this growth inhibitory effect of chelidonine was induced through apoptosis. We found that chelidonine treatment upregulated mRNA levels and transcription factor activity in both cell lines. Increases in protein expression levels of p53, GADD45A, p21 and cleaved caspase-3 were also observed, with more distinct changes in MIA PaCa-2 cells compared to the BxPC-3 cells. These results suggest that chelidonine induces pancreatic cancer apoptosis through the p53 and GADD45A pathways. Our findings provide new insights into the use of chelidonine for the treatment of pancreatic cancer.

Keywords: GADD45a; apoptosis; chelidonine; p53; pancreatic cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Benzophenanthridines / pharmacology
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Cell Proliferation
  • Humans
  • Pancreatic Neoplasms* / drug therapy
  • Tumor Suppressor Protein p53* / genetics

Substances

  • Benzophenanthridines
  • Cell Cycle Proteins
  • GADD45A protein, human
  • Tumor Suppressor Protein p53
  • chelidonine