Betacyanins enhance vitexin-2-O-xyloside mediated inhibition of proliferation of T24 bladder cancer cells.
Betacyanins (BC) were purified from beetroot (Beta vulgaris var. rubra L.) and tested, alone or in combination with vitexin-2-O-xyloside (XVX) from Beta vulgaris var. cicla L., for their ability to reduce the proliferation rate in T24 bladder cancer cells. Combination of BC and XVX exhibited a synergistic effect concerning the inhibition of proliferation in T24 cancer cells at 24 and 48 h but not after 72 h of incubation. The induction of apoptosis was evidenced by means of fluorescence activated cell sorting (FACS) analysis, as well as through the increase in caspase 3 and 8 activities. Using RTqPCR experiments, it was shown that the combination of XVX + BC was able to enhance the expression levels of pro-apoptotic BAX and downregulate anti-apoptotic BIRC5 (survivin), as well as pro-survival CTNNB1 (β-catenin). The most evident effect of BC was the increase of the activity of caspase 8, leading to induction of extrinsic apoptosis. Moreover, XVX, BC and their combination showed no cytotoxic effect on normal human skin NCTC 2544 keratinocytes. These results demonstrated the efficacy and the mechanisms of the action of BC and XVX, extracted from edible plants, and suggested that a diet or a nutrition supplement, enriched with these bioactive molecules, could be used in the prevention of human bladder cancer.
Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Urbino, Italy. paolino.ninfali@uniurb.it.
E S
ES
Scarpa
Department of Clinical Sciences, Polytechnic University of Marche, Ancona, Italy and New York-Marche Structural Biology Center (NY-MaSBiC), Polytechnic University of Marche, Ancona, Italy.
M
M
Emanuelli
Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Urbino, Italy. paolino.ninfali@uniurb.it.
A
A
Frati
Department of Clinical Sciences, Polytechnic University of Marche, Ancona, Italy and New York-Marche Structural Biology Center (NY-MaSBiC), Polytechnic University of Marche, Ancona, Italy.
V
V
Pozzi
Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Urbino, Italy. paolino.ninfali@uniurb.it.
E
E
Antonini
Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Urbino, Italy. paolino.ninfali@uniurb.it.
G
G
Diamantini
Department of Clinical Sciences, Polytechnic University of Marche, Ancona, Italy.
G
G
Di Ruscio
Department of Clinical Sciences, Polytechnic University of Marche, Ancona, Italy.
D
D
Sartini
Department of Clinical Sciences, Polytechnic University of Marche, Ancona, Italy.
T
T
Armeni
Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Urbino, Italy. paolino.ninfali@uniurb.it.
F
http://orcid.org/0000-0001-9836-1821
F
Palma
Department of Biomolecular Sciences, University of Urbino "Carlo Bo", Urbino, Italy. paolino.ninfali@uniurb.it.
P
P
Ninfali
D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis; D027461:Beta vulgaris / Q000737:chemistry; D050859:Betacyanins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D015536:Down-Regulation; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D006027:Glycosides / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure
D016588:Anticarcinogenic Agents; D050859:Betacyanins; D005419:Flavonoids; D006027:Glycosides; C586695:vitexin-2-O-xyloside