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The Phytochemical Indicaxanthin Synergistically Enhances Cisplatin-Induced Apoptosis in HeLa Cells via Oxidative Stress-Dependent p53/p21 waf1 Axis.
- Source :
-
Biomolecules [Biomolecules] 2020 Jul 02; Vol. 10 (7). Date of Electronic Publication: 2020 Jul 02. - Publication Year :
- 2020
-
Abstract
- Combining phytochemicals with chemotherapics is an emerging strategy to treat cancer to overcome drug toxicity and resistance with natural compounds. We assessed the effects of indicaxanthin (Ind), a pigment obtained from Opuntia ficus-indica (L. Mill) fruit, combined with cisplatin (CDDP) against cervical cancer cells (HeLa). Measured cell viability via Trypan blue assay; cell morphology via fluorescence microscopy; apoptosis, cell cycle, mitochondrial membrane potential (MMP) and cell redox balance via flow-cytometry; expression levels of apoptosis-related proteins via western blot. Cell viability assays and Chou-Talalay plot demonstrated that the combination of CDDP and Ind had synergistic cytotoxic effects. Combined treatment had significant effects ( p < 0.05) on phosphatidylserine externalization, cell morphological changes, cell cycle arrest, fall in MMP, ROS production and GSH decay compared with the individual treatment groups. Bax, cytochrome c, p53 and p21 <superscript>waf1</superscript> were over-expressed, while Bcl-2 was downregulated. Pre-treatment with N-acetyl-l-cysteine abolished the observed synergistic effects. We also demonstrated potentiation of CDDP anticancer activity by nutritionally relevant concentrations of Ind. Oxidative stress-dependent mitochondrial cell death is the basis of the chemosensitizing effect of Ind combined with CDDP against HeLa cancer cells. ROS act as upstream signaling molecules to initiate apoptosis via p53/p21 <superscript>waf1</superscript> axis. Ind can be a phytochemical of interest in combo-therapy.
- Subjects :
- Cell Proliferation drug effects
Cell Survival drug effects
Drug Synergism
Gene Expression Regulation, Neoplastic drug effects
HeLa Cells
Humans
Membrane Potential, Mitochondrial drug effects
Oxidative Stress drug effects
Proto-Oncogene Proteins c-bcl-2 metabolism
Reactive Oxygen Species metabolism
Antineoplastic Combined Chemotherapy Protocols pharmacology
Betaxanthins pharmacology
Cisplatin pharmacology
Cyclin-Dependent Kinase Inhibitor p21 metabolism
Pyridines pharmacology
Tumor Suppressor Protein p53 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2218-273X
- Volume :
- 10
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Biomolecules
- Publication Type :
- Academic Journal
- Accession number :
- 32630700
- Full Text :
- https://doi.org/10.3390/biom10070994