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.
Peroxisome Proliferator-activated Receptor Gamma Activation Induces Cell Cycle Arrest via the p53-independent Pathway in Human Anaplastic Thyroid Cancer Cells