Antiproliferative Effects of Cynaropicrin on Anaplastic Thyroid Cancer Cells.
Antineoplastic Agents, Phytogenic
/ therapeutic use
Antioxidants
/ pharmacology
Cell Cycle Checkpoints
/ drug effects
Cell Line, Tumor
Cell Survival
/ drug effects
Humans
Lactones
/ therapeutic use
Lipid Peroxidation
/ drug effects
Malondialdehyde
/ metabolism
NF-kappa B
/ drug effects
Phosphorylation
/ drug effects
Reactive Oxygen Species
/ metabolism
STAT3 Transcription Factor
/ drug effects
Sesquiterpenes
/ therapeutic use
Thyroid Carcinoma, Anaplastic
/ drug therapy
Thyroid Neoplasms
/ drug therapy
Artichoke leaves
Lipid peroxidation
STAT3
cynaropicrin
proliferation
sesquiterpenes
thyroid cancer.
Journal
Endocrine, metabolic & immune disorders drug targets
ISSN: 2212-3873
Titre abrégé: Endocr Metab Immune Disord Drug Targets
Pays: United Arab Emirates
ID NLM: 101269157
Informations de publication
Date de publication:
2019
2019
Historique:
received:
16
10
2017
revised:
14
06
2018
accepted:
14
06
2018
pubmed:
29
9
2018
medline:
18
5
2019
entrez:
29
9
2018
Statut:
ppublish
Résumé
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. 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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
METHODS
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 30264682
pii: EMIDDT-EPUB-93299
doi: 10.2174/1871530318666180928153241
doi:
Substances chimiques
Antineoplastic Agents, Phytogenic
0
Antioxidants
0
Lactones
0
NF-kappa B
0
Reactive Oxygen Species
0
STAT3 Transcription Factor
0
STAT3 protein, human
0
Sesquiterpenes
0
Malondialdehyde
4Y8F71G49Q
cynaropicrin
M9233789I9
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
59-66Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.