» Articles » PMID: 36555736

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

Overview
Journal Int J Mol Sci
Publisher MDPI
Date 2022 Dec 23
PMID 36555736
Authors
Affiliations
Soon will be listed here.
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 + 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.

References
1.
Kosumi K, Masugi Y, Yang J, Qian Z, Kim S, Li W . Tumor SQSTM1 (p62) expression and T cells in colorectal cancer. Oncoimmunology. 2017; 6(3):e1284720. PMC: 5384412. DOI: 10.1080/2162402X.2017.1284720. View

2.
Al-Obeed O, El-Obeid A, Matou-Nasri S, Vaali-Mohammed M, Alhaidan Y, Elwatidy M . Herbal melanin inhibits colorectal cancer cell proliferation by altering redox balance, inducing apoptosis, and modulating MAPK signaling. Cancer Cell Int. 2020; 20:126. PMC: 7161222. DOI: 10.1186/s12935-020-01206-x. View

3.
McComb S, Chan P, Guinot A, Hartmannsdottir H, Jenni S, Dobay M . Efficient apoptosis requires feedback amplification of upstream apoptotic signals by effector caspase-3 or -7. Sci Adv. 2019; 5(7):eaau9433. PMC: 6669006. DOI: 10.1126/sciadv.aau9433. View

4.
Gasiorkiewicz B, Koczurkiewicz-Adamczyk P, Piska K, Pekala E . Autophagy modulating agents as chemosensitizers for cisplatin therapy in cancer. Invest New Drugs. 2020; 39(2):538-563. PMC: 7960624. DOI: 10.1007/s10637-020-01032-y. View

5.
Emran T, Shahriar A, Mahmud A, Rahman T, Abir M, Siddiquee M . Multidrug Resistance in Cancer: Understanding Molecular Mechanisms, Immunoprevention and Therapeutic Approaches. Front Oncol. 2022; 12:891652. PMC: 9262248. DOI: 10.3389/fonc.2022.891652. View