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Phytomedicine. 2018 Nov 15;50:19-24. doi: 10.1016/j.phymed.2018.09.171. Epub 2018 Sep 18.

Indicaxanthin from Opuntia Ficus Indica (L. Mill) impairs melanoma cell proliferation, invasiveness, and tumor progression.

Author information

1
Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Università di Palermo, Via Archirafi 28, 90123 Palermo, Italy.
2
Dipartimento di Farmacia, Scuola di Medicina, Università di Napoli Federico II, Via Montesano 49, 80131 Napoli, Italy.
3
Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche, Università di Palermo, Via Archirafi 28, 90123 Palermo, Italy. Electronic address: ianaro@unina.it.

Abstract

BACKGROUND:

A strong, reciprocal crosstalk between inflammation and melanoma has rigorously been demonstrated in recent years, showing how crucial is a pro-inflammatory microenvironment to drive therapy resistance and metastasis.

PURPOSE:

We investigated on the effects of Indicaxanthin, a novel, anti-inflammatory and bioavailable phytochemical from Opuntia Ficus Indica fruits, against human melanoma both in vitro and in vivo.

STUDY DESIGN AND METHODS:

The effects of indicaxanthin were evaluated against the proliferation of A375 human melanoma cell line and in a mice model of cutaneous melanoma. Cell proliferation was assessed by MTT assay, apoptosis by Annexin V-Fluorescein Isothiocyanate/Propidium Iodide staining, protein expression by western blotting, melanoma lesions were subcutaneously injected in mice with B16/F10 cells, chemokine release was quantified by ELISA.

RESULTS:

Data herein presented demonstrate that indicaxanthin effectively inhibits the proliferation of the highly metastatic and invasive A375 cells as shown by growth inhibition, apoptosis induction and cell invasiveness reduction. More interestingly, in vitro data were paralleled by those in vivo showing that indicaxanthin significantly reduced tumor development when orally administered to mice. The results of our study also clarify the molecular mechanisms underlying the antiproliferative effect of indicaxanthin, individuating the inhibition of NF-κB pathway as predominant.

CONCLUSION:

In conclusion, we demonstrated that indicaxanthin represents a novel phytochemical able to significantly inhibit human melanoma cell proliferation in vitro and to impair tumor progression in vivo. When considering the resistance of melanoma to the current therapeutical approach and the very limited number of phytochemicals able to partially counteract it, our findings may be of interest to explore indicaxanthin potential in further and more complex melanoma studies in combo therapy, i.e. where different check points of melanoma development are targeted.

KEYWORDS:

Apoptosis; Bcl-2, B cell lymphoma gene-2 (Bcl-2); CXCL1, chemokine (C-X-C motif) ligand 1; Indicaxanthin; Inflammation; List of Abbrevations: AxV-FITC, annexin V-fluorescein isothiocyanate; MTT, 3-[4,5-dimethyltiazol-2-yl]-2,5-diphenyl tetrazolium bromide; Melanoma; NF-κB, nuclear factor kappa B; NHEM, normal human epidermal melanocytes; Opuntia Ficus Indica (L.Mill); PI, propidium iodide PI; PhC, phytochemicals; Phytochemical; c-FLIP, FLICE-inhibitory protein

PMID:
30466978
DOI:
10.1016/j.phymed.2018.09.171
[Indexed for MEDLINE]

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