Antiproliferative Effects of Cynaropicrin on Anaplastic Thyroid Cancer Cells.

BACKGROUND: The sesquiterpene lactone cynaropicrin, a major constituent of the artichoke leaves extracts, has shown several biologic activities in many preclinical experimental models, including anti-proliferative effects. OBJECTIVE: Herein we evaluated the effects of cynaropicrin on the growth of three human anaplastic thyroid carcinoma cell lines, investigating the molecular mechanism underlying its action. METHOD: MTT assay was used to evaluate the viability of CAL-62, 8505C and SW1736 cells, and flow cytometry to analyse cell cycle distribution. Western blot was performed to detect the levels of STAT3 phosphorylation and NFkB activation. Antioxidant effects were analyzed by measuring the reactive oxygen species and malonyldialdehyde dosage was used to check the presence of lipid peroxidation. RESULTS: Viability of CAL-62, 8505C and SW1736 cells was significantly reduced by cynaropicrin in a dose- and time-dependent way, with an EC50 of about 5 µM observed after 48 h of treatment with the compound. Cellular growth inhibition was accompanied both by an arrest of the cell cycle, mainly in the G2/M phase, and the presence of a significant percentage of necrotic cells. After 48 h of treatment with 10 µM of cynaropicrin, a reduced nuclear expression of NFkB and STAT3 phosphorylation were also revealed. Moreover, we observed an increase in lipid peroxidation, without any significant effect on the reactive oxygen species production. CONCLUSION: These results demonstrate that cynaropicrin reduces the viability and promotes cytotoxic effects in anaplastic thyroid cancer cells associated with reduced NFkB expression, STAT3 phosphorylation and increased lipid peroxidation. Further characterization of the properties of this natural compound may open the way for using cynaropicrin as an adjuvant in the treatment of thyroid cancer.

Chemical Characterization and Biological Activities of Phenolic-Rich Fraction from Cauline Leaves of Isatis tinctoria L. (Brassicaceae) Growing in Sicily, Italy.

The present work focused on the evaluation of the antioxidant and cytotoxic activities of the phenolic-rich fraction (ItJ-EAF) obtained from cauline leaves collected in January from Isatis tinctoria L. (Brassicaceae) growing wild around Acireale (Sicily, Italy). The total phenolic, flavonoid, and condensed tannin contents of the fraction were determined spectrophotometrically, whereas the phenolic profile was assessed by HPLC-PDA/ESI-MS analysis. A total of 20 compounds were positively identified and twelve out of them were never previously reported in I. tinctoria leaves. The fraction exhibited good radical scavenging activity in DPPH test (IC50  = 0.6657 ± 0.0024 mg/ml) and reducing power (3.87 ± 0.71 ASE/ml), whereas, it neither showed chelating activity nor was able to counteract H2 O2 induced oxidative stress damage in Escherichia coli. The antiproliferative effect was evaluated in vitro on two human anaplastic thyroid carcinoma cell lines (CAL-62 and 8505C) by MTT assay. At the highest tested concentration ItJ-EAF significantly reduced (80%) the growth of CAL-62 cells. No cytotoxicity against Artemia salina was observed. It can be concluded that I. tinctoria cauline leaves represent a source of phenolic compounds which could be potentially used as chemopreventive or adjuvant agents against cancer.

Flavonoid Fraction of Citrus reticulata Juice Reduces Proliferation and Migration of Anaplastic Thyroid Carcinoma Cells.

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.

Beneficial effects of the olive oil phenolic components oleuropein and hydroxytyrosol: focus on protection against cardiovascular and metabolic diseases.

The overall health beneficial action of olive oil phenolic components is well established. Recent studies have elucidated the biological effects of two isolated compounds, namely oleuropein and hydroxytyrosol, with particular attention on their antioxidant activity. Thus, a protective action has been demonstrated in preclinical studies against several diseases, especially cardiovascular and metabolic disorders. The present review will describe the biological effects of oleuropein and hydroxytyrosol, with particular attention on the molecular mechanism underlying the protective action on cardiovascular and metabolic alterations, as demonstrated by in vitro and in vivo experimental studies performed with the isolated compounds.