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Inhibition of Cancer Stem-Like Phenotype by Curcumin and Deguelin in CAL-62 Anaplastic Thyroid Cancer Cells
Mehmet A Kocdor1, Hakan Cengiz2, Halil Ates3
1Department of Surgery, Breast and Endocrine Surgery Unit, Dokuz Eylul University Hospital, 35340 Inciralti, Izmir, Turkey.
Background:
Anaplastic Thyroid Cancer (ATC) is one of the most lethal and aggressive human malignancies. Studies have shown that Cancer Stem-Cell (CSC) phenotype is mainly responsible for ATC aggressiveness. Cytostatic compounds are mostly ineffective because of multidrug resistance mechanisms driven by the CSC phenotype. Taxanes have limited efficacy. Recently, CSC inhibition using plant-derived, less toxic compounds, which have anti-cancer efficacy, has become a novel treatment modality. The aim of the study was to evaluate the anti-cancer activity of two natural compounds (curcumin and deguelin) on ATC cells and their CSC properties. In addition, the efficacies of these compounds were compared with that of docetaxel.
Methods:
Besides control, five treatment groups were formed. ATC cells (CAL-62) were treated with curcumin, deguelin, docetaxel, and their combinations (curcumin+docetaxel, deguelin+docetaxel) at previously determined IC50 doses. Stemness was analyzed by quantitative estimation of sphere formation in matrigel, expression of several cell surface markers (CD133, CD90, Nanog, and OCT3/4) using flow cytometry, and quantification of the hypoxic status [Oxidative Stress Index (OSI) and Superoxide Dismutase (SOD) activity]. The anti-cancer efficacies of these compounds and their combinations were evaluated by determining the alterations in the cell cycle, apoptosis, and tumoral cell migration.
Results:
Both the natural compounds (particularly curcumin) significantly suppressed the spheroid formation and cellular motility in matrigel as well as suppressed the accumulation of cells in the G0/1 phase, in which the maximum CSC activity is observed. The compounds did not suppress the expression of CSC markers, but twothirds of the cells expressed CD90. Deguelin was found to be particularly effective in inducing apoptosis similar to docetaxel at IC50 concentrations. Curcumin reduced the OSI and deguelin enhanced the SOD activity, even in docetaxel pre-treated cells.
Conclusion:
A large proportion of anaplastic tumors might consist of heterogeneous CSC population. Curcumin and deguelin have anti-cancer and several anti-stem cell activities against ATC cells. These natural compounds are capable of altering the aggressive behavior of ATC cells through the inhibition of the CSC phenotype. As a novel therapeutic target, CD90 should be investigated in other ATC cell lines and in vivo models.
Insights
Curcumin and deguelin show anti-cancer and anti-stem cell properties against Anaplastic Thyroid Cancer (ATC). These natural compounds can alter aggressive ATC cell behavior by inhibiting the Cancer Stem-Cell (CSC) phenotype, offering a potential new therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Natural Products Chemistry
Background:
- Anaplastic Thyroid Cancer (ATC) is highly aggressive and lethal, with Cancer Stem-Cell (CSC) phenotype driving its malignancy.
- Multidrug resistance mechanisms in CSCs limit the efficacy of conventional cytostatic drugs and taxanes.
- Natural, less toxic compounds offer a novel therapeutic approach by targeting CSCs.
Purpose of the Study:
- To evaluate the anti-cancer and anti-CSC activities of curcumin and deguelin on ATC cells.
- To compare the efficacy of these natural compounds with docetaxel.
- To investigate the effects on CSC properties, including sphere formation, marker expression, and hypoxic status.
Main Methods:
- Anaplastic Thyroid Cancer (CAL-62) cells were treated with curcumin, deguelin, and docetaxel at IC50 doses.
- Sphere formation, cell surface marker expression (CD133, CD90, Nanog, OCT3/4), and hypoxic status (OSI, SOD) were analyzed.
- Cell cycle, apoptosis, and migration were assessed to evaluate anti-cancer efficacy.
Main Results:
- Curcumin and deguelin significantly reduced sphere formation and cell migration, and altered cell cycle progression.
- While not suppressing CSC marker expression, CD90 was notably expressed in two-thirds of treated cells.
- Deguelin induced apoptosis similarly to docetaxel; curcumin reduced OSI and deguelin enhanced SOD activity.
Conclusions:
- Curcumin and deguelin exhibit significant anti-cancer and anti-stem cell activities against ATC.
- These natural compounds can modify aggressive ATC cell behavior by inhibiting the CSC phenotype.
- CD90 presents a potential therapeutic target for ATC and warrants further investigation in other cell lines and in vivo models.
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