In vitro studies on new therapeutic approaches for human thyroid cancer

Abstract

Thyroid cancer is the most prevalent endocrine malignancy, and its incidence has been increasing. It has been reported that Type I receptor for transferrin (TfR1/CD71) is expressed on malignant cells at levels several fold higher than those on normal cells and its expression can be correlated with tumor stage or cancer progression. In previous studies, an aberrant expression of this receptor in thyroid carcinomas was found [Magro et al., 2011]. The aim of the study was to assess the expression of TfR1 in two cancer cell lines, FTC-133 and 8305C, as representative of follicular and anaplastic thyroid human cancer, respectively. The effects of down-regulation of endogenous TfR1 following transfection with the siRNA oligonucleotide, the changes in cell growth and the activation of Erk1/Erk2 pathway were also evaluated. The correlation between apoptosis and UVA induced ultra-weak photon emission (Delayed Luminescence, DL) from tumor thyroid cell lines was investigated. In particular, it has been studied the effects of Berberine, an alkaloid that has been reported to have anticancer activities, on FTC-133 and 8305C cancer cell lines. Our results showed that TfR1 appeared expressed at high levels in both thyroid cancer cell lines, even if it was more evident in the anaplastic ones. TfR1 was prevalently localized in the cytosol and in the mitochondria in the thyroid follicular cell lines, whether in the anaplastic cancer cell lines it was also localized into the nuclear compartments. In parallel, an activation of Erk1/Erk2 pathway in the both cell lines was observed. Our findings indicate that TfR1 plays a fundamental role in thyroid cancer progression promoting cell signaling probably thought Erk1/Erk2 pathway, suggesting also that it might represent an important target for thyroid cancer therapy. The results show that Berberine is able to arrest cell cycle and activate apoptotic pathway as shown in both cell lines by DNA fragmentation, Caspase-3 cleavage, p53 and p27 protein overexpression. In parallel, changes in DL spectral components after Berberine treatment support the hypothesis that DL from human cells originates mainly from mitochondria, since Berberine acts especially at the mitochondrial level. In addition the strong decrease of DL blue component for both cell lines may be a hallmark of induced apoptosis, while different response in the red spectral range may be ascribed to a different iron homeostasis in the cell lines. In conclusion, the silencing of TfR1 and the Berberine may represent a novel anticancer treatment of poorly differentiated or anaplastic thyroid cancers.