Prunus spinosa Extract Sensitized HCT116 Spheroids to 5-Fluorouracil Toxicity, Inhibiting Autophagy

Int J Mol Sci. 2022 Dec 17;23(24):16098. doi: 10.3390/ijms232416098.

Abstract

Autophagy is a lysosomal degradation and recycling process involved in tumor progression and drug resistance. The aim of this work was to inhibit autophagy and increase apoptosis in a 3D model of human colorectal cancer by combined treatment with our patented natural product Prunus spinosa + nutraceutical activator complex (PsT + NAC®) and 5-fluorouracil (5-FU). By means of cytotoxic evaluation (MTT assay), cytofluorimetric analysis, light and fluorescence microscopy investigation and Western blotting evaluation of the molecular pathway PI3/AKT/mTOR, Caspase-9, Caspase-3, Beclin1, p62 and LC3, we demonstrated that the combination PsT + NAC® and 5-FU significantly reduces autophagy by increasing the apoptotic phenomenon. These results demonstrate the importance of using non-toxic natural compounds to improve the therapeutic efficacy and reduce the side effects induced by conventional drugs in human colon cancer.

Keywords: 5-fluorouracil; Prunus spinosa; apoptosis; autophagy; colorectal cancer; drug resistance; spheroids.

MeSH terms

  • Antineoplastic Agents* / pharmacology
  • Apoptosis
  • Autophagy
  • Cell Line, Tumor
  • Colonic Neoplasms* / pathology
  • Fluorouracil / pharmacology
  • Fluorouracil / therapeutic use
  • Humans
  • Prunus*

Substances

  • Fluorouracil
  • Antineoplastic Agents

Grants and funding

This research received no external funding.