The Effects of Tetrahydrocurcumin on Adriamycin and Taxane resistance in Anaplastic Thyroid Cancer Cells

Abstract

Purpose Anaplastic thyroid cancer (ATC) is rare but one of the most lethal human malignancy. Despite the advances in cancer treatments, ATC remained incurable due to a lack of effective treatments. ATC cells display resistance against all cytostatics. Adriamycin and taxanes have been used with limited efficacy. There is an urgent need for new treatments and less toxic substances that will enhance the effectiveness of current treatments. One of the most effective curcumin derivative, tetrahydrocurcumin (THC), appears to have several anti-cancer and anti-MDR (multidrug resistance) actions. Thus, we aimed to compare the anti-cancer efficacy of THC with adriamycin and docetaxel, as well as evaluate the anti-MDR action of two drugs in ATC cell lines, if any. Methods We used MTT test to find the IC50 values for Adriamycin (Adr), docetaxel (Doce) and THC (Cur). The cells were treated with IC50 and half-IC50 (IC25) doses. IC25 doses were also used for drug combinations. Wound healing assay, spheroid formation in soft agar, oxidative stress analysis, flow-cytometrically apoptosis, and multidrug resistance activity factor analysis (MAF) for MDR1 (P-gp), MRP1/2, BCRP expressions were performed in both cell lines. Results THC was more potent than docetaxel and adriamycin on cell migration, spheroid formation, anti-oxidant capacity, and apoptosis induction at LD50 dose in both cell lines. THC-induced MAF suppression was found particularly for MDR1 in both cell lines. Whereas adriamycin and docetaxel treatments lead to increased MRP1/2 and BCRP expressions. THC suppressed these actions dose dependent manner. Conclusion THC can modify MDR protein expressions and stem cell properties, which can increase the efficacy of doxorubicin and adriamycin in treating anaplastic thyroid cancer. THC has anti-cancer potential that is comparable to these two cytostatics. Curcumin could be considered an adjunctive component of the ATC treatment.