Prunus spinosa Extract Sensitized HCT116 Spheroids to 5-Fluorouracil Toxicity, Inhibiting Autophagy.
Maria CondelloRosa VonaStefania MeschiniPublished in: International journal of molecular sciences (2022)
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.
Keyphrases
- cell death
- cell cycle arrest
- endoplasmic reticulum stress
- oxidative stress
- signaling pathway
- induced apoptosis
- endothelial cells
- single molecule
- transcription factor
- cell proliferation
- induced pluripotent stem cells
- pi k akt
- anti inflammatory
- south africa
- optical coherence tomography
- mass spectrometry
- single cell
- immune response
- combination therapy
- replacement therapy
- drug induced
- nuclear factor