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Melanoma Inhibition by Anthocyanins Is Associated with the Reduction of Oxidative Stress Biomarkers and Changes in Mitochondrial Membrane Potential

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Abstract

Anthocyanins are water soluble pigments which have been proved to exhibit health benefits. Several studies have investigated their effects on several types of cancer, but little attention has been given to melanoma. The phytochemical content of nine different berry samples was assessed by liquid chromatography followed by electrospray ionization mass spectrometry (LC-ESI+-MS). Twenty-six anthocyanins were identified, after a previous C18 Sep-pak clean-up procedure. Chokeberry and red grape anthocyanins rich extracts (C-ARE and RG-ARE) were selected to be tested on normal and melanoma cell lines, due to their different chemical pattern. C-ARE composition consists of cyanidin aglycone glycosylated with different sugars; while RG-ARE contains glucosylated derivatives of five different aglycones. Both C-ARE and RG-ARE anthocyanins reduced proliferation, increased oxidative stress biomarkers and diminished mitochondrial membrane potential in melanoma cells, having no negative influence on normal cells. A synergistic response may be attributed to the five different aglycones present in RG-ARE, which proved to exert greater effects on melanoma cells than the mixture of cyanidin derivatives with different sugars (C-ARE). In conclusion, C-ARE and RG-ARE anthocyanins may inhibit melanoma cell proliferation and increase the level of oxidative stress, with opposite effect on normal cells. Therefore, anthocyanins might be recommended as active ingredients for cosmetic and nutraceutical industry.

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Abbreviations

AREs:

Anthocyanin rich extract

LC–ESI-MS:

Liquid chromatography followed by electrospray ionization mass spectrometry

DMEM:

Dulbecco’s Modified Eagle Medium

FBS:

Fetal Bovine Serum

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide

RG-ARE:

red grape anthocyanin rich extract

C-ARE:

chokeberry anthocyanin rich extract

Cy-3-O-glu:

Cyanidin-3-O-glucoside

Cy-3-O-ara:

Cyanidin-3-O-arabinoside

Cy-3-O- mal-glu:

Cyanidin-3-O-malonyl-glucoside

Cy-3-O- dio-glu:

Cyanidin-3-O- dioxalylglucoside

Cy-3-O-rut:

Cyanidin-3-O-rutinoside

Peo-3-O-glu:

Peonidin-3-O-glucoside

Peo-3-O-rut:

Peonidin-3-O-rutinoside

Delp-3-O-gal:

Delphinidin-3-O-galactoside

Delp-3-O-glu:

Delphinidin-3-O-glucoside

Cy-3-O-gal:

Cyanidin-3-O-galactoside

Delp-3-O-ara:

Delphinidin-3-O-arabinoside

Pet-3-O-gal:

Petunidin-3-O-galactoside

Peo-3-O-gal:

Peonidin-3-O-galactoside

Pet-3-O-ara:

Petunidin-3-O-arabinoside

Mal-3-O-gala:

Malvidin-3-O-galactoside

Mal-3-O-glu:

Malvidin-3-O-glucoside

Mal-3-O-ara:

Malvidin-3-O-arabinoside

Pet-3-O-glu:

Petunidin-3-O-glucoside

Pel-3-O-glu:

Pelargonidin-3-O-glucoside

Delp-3-O-rut:

Delphinidin-3-O-rutinoside

Cy-3-O-xyl:

Cyanidin-3-O-xyloside

Malvidin-3-O-glucoside-4-vinylcathecol:

Mal-3-O-glue 4 vinylcathecol

Malvidin-6-acetyl-3-galactoside:

Mal-6-acetyl-3-gal

Cy-3-O-sam:

Cyanidin-3-O-sambubioside

Pel-3-O-sam:

Pelargonidin-3-O-sambubioside

Pet-3-(6-O-p-coumarylglu):

Petunidin-3-(6-O-p-coumarylglucoside)

LDH:

Lactate dehydrogenase

MDA:

Malondialdehyde

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Acknowledgements

This paper was supported by UEFISCDI project number PN-II-RU-TE-2014-4-0944, 16/01.10.2015. The authors are grateful to biologist Raluca Ghiman for performing the graphical abstract.

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Authors and Affiliations

  1. University of Agricultural Science and Veterinary Medicine, 400372, Cluj-Napoca, Romania

    Zoriţa Diaconeasa, Dumitriţa Ruginǎ, Loredana Leopold, Andreea Stǎnilǎ, Carmen Socaciu, Flaviu Tăbăran & Adela Pintea

  2. Canakkale Onsekiz Mart University, 17020, Canakkale, Turkey

    Huseyin Ayvaz

  3. Babeș-Bolyai University, 400084, Cluj-Napoca, Romania

    Lavinia Luput

  4. Iuliu Hatieganu University of Medicine and Pharmacy, 400006, Cluj-Napoca, Romania

    Diana Carla Mada

  5. Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK

    Andrew Jefferson

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  1. Zoriţa Diaconeasa
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Correspondence to Dumitriţa Ruginǎ.

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Diaconeasa, Z., Ayvaz, H., Ruginǎ, D. et al. Melanoma Inhibition by Anthocyanins Is Associated with the Reduction of Oxidative Stress Biomarkers and Changes in Mitochondrial Membrane Potential. Plant Foods Hum Nutr 72, 404–410 (2017). https://doi.org/10.1007/s11130-017-0638-x

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