High doses of hydroxytyrosol induce apoptosis in papillary and follicular thyroid cancer cells.
OBJECTIVE
Recent evidences indicates that hydroxytyrosol, one of the main olive oil phenols, possess antitumor effects because of its pro-oxidant properties and the capacity to inhibit proliferation and to promote apoptosis in several tumor cell lines, although most of the results were obtained for breast and digestive systems cancers.


METHODS
In this study, we evaluated the activities of hydroxytyrosol against papillary (TPC-1, FB-2) and follicular (WRO) thyroid cancer cell lines.


RESULTS
Cellular viability revealed that high doses of hydroxytyrosol reduced cancer cells viability concomitantly with a reduction of cyclin D1 expression and an up-regulation of cell cycle key modulator p21 levels. In the same experimental conditions, Annexin V-PI staining and DNA laddering revealed that hydroxytyrosol exerts proapoptotic effects on papillary and follicular cancer cells. Furthermore, by Western blot analysis, we observed that hydroxytyrosol treatment reduced thyroid cancer cells viability by promoting apoptotic cell death via intrinsic pathway.


CONCLUSIONS
Collectively, our results demonstrated for the first time that in thyroid cancer cells hydroxytyrosol promoted apoptosis at higher doses with respect to other cancer cells lines. Therefore, further studies will reveal the mechanisms by which thyroid cancer cells are more resistant to the proapoptotic effect exerted by hydroxytyrosol as well as the potential application as novel target therapeutic in thyroid cancer.
"Kidney and Transplantation" Research Center, UOC Nephrology, Dialysis and Transplantation, Annunziata Hospital, F. Migliori, 1, 87100, Cosenza, CS, Italy.
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Toteda
"Kidney and Transplantation" Research Center, UOC Nephrology, Dialysis and Transplantation, Annunziata Hospital, F. Migliori, 1, 87100, Cosenza, CS, Italy.
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Lupinacci
"Kidney and Transplantation" Research Center, UOC Nephrology, Dialysis and Transplantation, Annunziata Hospital, F. Migliori, 1, 87100, Cosenza, CS, Italy.
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Vizza
"Kidney and Transplantation" Research Center, UOC Nephrology, Dialysis and Transplantation, Annunziata Hospital, F. Migliori, 1, 87100, Cosenza, CS, Italy.
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Bonofiglio
Consiglio per la Ricerca in Agricoltura e l'Analisi dell'Economia Agraria (CREA)-Olive Growing and Olive Oil Industry Research Centre, Rende, CS, Italy.
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Perri
"Kidney and Transplantation" Research Center, UOC Nephrology, Dialysis and Transplantation, Annunziata Hospital, F. Migliori, 1, 87100, Cosenza, CS, Italy.
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Bonofiglio
"Kidney and Transplantation" Research Center, UOC Nephrology, Dialysis and Transplantation, Annunziata Hospital, F. Migliori, 1, 87100, Cosenza, CS, Italy.
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Lofaro
"Kidney and Transplantation" Research Center, UOC Nephrology, Dialysis and Transplantation, Annunziata Hospital, F. Migliori, 1, 87100, Cosenza, CS, Italy.
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La Russa
"Kidney and Transplantation" Research Center, UOC Nephrology, Dialysis and Transplantation, Annunziata Hospital, F. Migliori, 1, 87100, Cosenza, CS, Italy.
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Leone
"Kidney and Transplantation" Research Center, UOC Nephrology, Dialysis and Transplantation, Annunziata Hospital, F. Migliori, 1, 87100, Cosenza, CS, Italy.
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Gigliotti
Laboratory X-life, ARPAB-CRM, Matera Hospital, Matera, Italy.
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Cifarelli
"Kidney and Transplantation" Research Center, UOC Nephrology, Dialysis and Transplantation, Annunziata Hospital, F. Migliori, 1, 87100, Cosenza, CS, Italy. anna_perri@yahoo.it.
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Perri
D018263:Adenocarcinoma, Follicular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002291:Carcinoma, Papillary / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000975:Antioxidants; C530104:CCND1 protein, human; D012333:RNA, Messenger; C005975:3,4-dihydroxyphenylethanol; D019938:Cyclin D1; D010626:Phenylethyl Alcohol
Apoptosis; Hydroxytyrosol; Nutrition; Olive oil; Thyroid cancer