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Chemopreventive effects of FITOPROT against 5-fluorouracil-induced toxicity in HaCaT cells
- Source :
- Life Sciences. 193:300-308
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- Aims This study evaluated the mechanisms involved in the chemopreventive effects of a mucoadhesive formulation (FITOPROT), containing curcuminoids from Curcuma longa L. (Zingiberaceae) and Bidens pilosa L. (Asteraceae) extract, against 5-FU-induced cellular toxicity using an in vitro oral mucositis model. Main methods Effects of FITOPROT on 5-FU-induced cytotoxicity in HaCaT and SSC-4 cells were evaluated by MTT assay. For mechanistic analyses, HaCaT cells were first pretreated with FITOPROT (0.005%) for 24 h followed by treatment with FITOPROT and simultaneously exposed to 5-FU (10 μg/mL) for additional 24 h. Key findings FITOPROT was able to protect HaCaT cells from 5-FU-triggered cell damage. Moreover, the FITOPROT + 5-FU association showed higher cytotoxic effects on SSC-4 cancer cells. Flow cytometry and/or fluorescence microscopy analysis showed FITOPROT was able to significantly reduce ROS generation and prevent mitochondrial changes in HaCaT cells. In addition, it avoided the release of cytochrome c from mitochondria to the cytoplasm in cells exposed to 5-FU, and restored their proliferative activity via Ki-67 expression. Furthermore, FITOPROT regulated 5-FU-induced oxidative stress via Nrf2 involvement. HaCaT cells pretreated/treated with FITOPROT also showed normal expression of TNF-R1 and NF-κB inflammatory proteins and decreased levels of pro-inflammatory cytokines (TNF, IL-1β, IL-6 and IL-8). Moreover, a high-resolution liquid chromatography-mass spectrometry analysis showed the presence of flavonoids rutin, glucoronylated quercetin and dimethylquercetin rutenoside in FITOPROT. Significance It was showed that FITOPROT, an antioxidant phytochemicals-rich mucoadhesive formulation, exerts chemopreventive effects against 5-FU-triggered toxicity through antioxidant and anti-inflammatory mechanisms and restoration of proliferative capacity in HaCaT cells.
- Subjects :
- Keratinocytes
0301 basic medicine
Cell Survival
Interleukin-1beta
Pharmacology
Protective Agents
medicine.disease_cause
Antioxidants
General Biochemistry, Genetics and Molecular Biology
Cell Line
Ligases
03 medical and health sciences
Curcuma
0302 clinical medicine
Cell Line, Tumor
medicine
Anticarcinogenic Agents
Humans
Cytotoxic T cell
MTT assay
General Pharmacology, Toxicology and Pharmaceutics
Cytotoxicity
Cell damage
Cell Proliferation
Flavonoids
Stomatitis
Interleukin-6
Tumor Necrosis Factor-alpha
Chemistry
NF-kappa B
General Medicine
medicine.disease
HaCaT
030104 developmental biology
030220 oncology & carcinogenesis
Cancer cell
Toxicity
Cytokines
Fluorouracil
Oxidative stress
Subjects
Details
- ISSN :
- 00243205
- Volume :
- 193
- Database :
- OpenAIRE
- Journal :
- Life Sciences
- Accession number :
- edsair.doi.dedup.....0fb5df0a83462f49d8bbca0a9d69ac2a