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Article

The Phytochemical Indicaxanthin Synergistically Enhances Cisplatin-Induced Apoptosis in HeLa Cells via Oxidative Stress-Dependent p53/p21waf1 Axis

Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Università di Palermo, 90123 Palermo, Italy
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Received: 27 May 2020 / Revised: 26 June 2020 / Accepted: 28 June 2020 / Published: 2 July 2020
(This article belongs to the Special Issue Biomolecules and Cancer Prevention)
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 p21waf1 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/p21waf1 axis. Ind can be a phytochemical of interest in combo-therapy. View Full-Text
Keywords: combo-therapy; oxidative stress; phytochemicals; indicaxanthin; Opuntia ficus indica (L. Mill); cancer; cisplatin combo-therapy; oxidative stress; phytochemicals; indicaxanthin; Opuntia ficus indica (L. Mill); cancer; cisplatin
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MDPI and ACS Style

Allegra, M.; D’Anneo, A.; Frazzitta, A.; Restivo, I.; Livrea, M.A.; Attanzio, A.; Tesoriere, L. The Phytochemical Indicaxanthin Synergistically Enhances Cisplatin-Induced Apoptosis in HeLa Cells via Oxidative Stress-Dependent p53/p21waf1 Axis. Biomolecules 2020, 10, 994. https://0-doi-org.brum.beds.ac.uk/10.3390/biom10070994

AMA Style

Allegra M, D’Anneo A, Frazzitta A, Restivo I, Livrea MA, Attanzio A, Tesoriere L. The Phytochemical Indicaxanthin Synergistically Enhances Cisplatin-Induced Apoptosis in HeLa Cells via Oxidative Stress-Dependent p53/p21waf1 Axis. Biomolecules. 2020; 10(7):994. https://0-doi-org.brum.beds.ac.uk/10.3390/biom10070994

Chicago/Turabian Style

Allegra, Mario, Antonella D’Anneo, Anna Frazzitta, Ignazio Restivo, Maria A. Livrea, Alessandro Attanzio, and Luisa Tesoriere. 2020. "The Phytochemical Indicaxanthin Synergistically Enhances Cisplatin-Induced Apoptosis in HeLa Cells via Oxidative Stress-Dependent p53/p21waf1 Axis" Biomolecules 10, no. 7: 994. https://0-doi-org.brum.beds.ac.uk/10.3390/biom10070994

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