Corilagin enhances the anti-tumor activity of 5-FU by downregulating the expression of GRP 78

Sci Rep. 2023 Dec 19;13(1):22661. doi: 10.1038/s41598-023-49604-1.

Abstract

Colorectal cancer is one of the most common malignancies worldwide. Although initially effective, patients who receive chemotherapy ultimately experience various complications and develop chemo-resistance, leading to cancer recurrence. Therefore, we aimed to find a drug with good efficacy and low toxicity that could enhance the treatment with 5-Fluorouracil (a commonly used clinical drug) and reduce its dosing. Corilagin, an anti-tumor natural product, has received widespread attention. Glucose regulated protein 78 (GRP78) is overexpressed in colorectal cancer cells and plays a key role in the proliferation, migration and drug resistance of cancer cells. Importantly, GRP78 can affect the apoptosis induced by 5-fluorouracil in CRC cells. In the present study, we determined the synergistic anti-tumor activity of the combination treatment by cell proliferation assay, apoptosis assay, fluorescent staining, cell cycle analysis, WB and PCR assays. This synergistic effect was associated with S-phase blockade, intracellular reactive oxygen species production and downregulation of GRP78. Taken together, our results indicate that Corilagin acts as a potentiator of 5-fluorouracil and may have therapeutic potential for patients with CRC.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation
  • Colorectal Neoplasms* / pathology
  • Drug Resistance, Neoplasm
  • Endoplasmic Reticulum Chaperone BiP*
  • Fluorouracil / therapeutic use
  • Humans
  • Neoplasm Recurrence, Local / drug therapy

Substances

  • Endoplasmic Reticulum Chaperone BiP
  • corilagin
  • Fluorouracil

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