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Abstract
Effects of flavonoids extracted from Citrus reticulata (mandarin) juice on proliferation and migration of 3 human anaplastic thyroid carcinoma (ATC) cell lines were evaluated. Flavonoid components of Mandarin juice extract (MJe) were analyzed by uHPLC. Proliferation of CAL-62, C-643, and 8505C cells, measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, was significantly reduced by MJe in a concentration- and time-dependent way, with maximal effect elicited at 0.5 mg/ml concentration after 48 h. Cytofluorimetric analysis showed a block in the G2/M phase of the cell cycle, accompanied by low cell mortality owed to autophagic death. The extract caused also a reduction of cell migration, associated with decreased activity of the metalloproteinase MMP-2. These findings demonstrate that the flavonoid fraction of mandarin juice exerts in vitro antiproliferative effects on ATC cells, associated with a reduction of migration, suggesting for such a functional food a potential use as adjuvant in the treatment of thyroid cancer.
ACKNOWLEDGMENTS
We thank Dr. Giovanni Toscano for his skillful technical assistance in the uHPLC analyses. Marilena Celano and Valentina Maggisano contributed equally to this article.
FUNDING
Research was supported by a grant from Sicily Region (PO FESR Sicilia 2007/2013, project ‘‘MEPRA’’, N. 133 of Linea d'Intervento.
SUPPLEMENTAL DATA
Supplemental data for this article can be accessed on the publisher's website.