Therapeutic Potential of Tetrahydrocurcumin Against Multidrug-resistant Anaplastic Thyroid Cancer Cells

Background Anaplastic thyroid cancer (ATC) remained incurable due to its aggressive tumoral behaviour and chemoresistancy to all cytostatics and some targeted therapeutics. Adriamycin and taxanes have been used with limited efficacy. As a natural curcumin derivative, Tetrahydrocurcumin (THC) appeared to have several anti-cancer and anti-MDR (multidrug resistance) properties in several cancers. Here, we aimed to compare the anti-cancer efficacy of THC with that of adriamycin and docetaxel, as well as to evaluate the anti-MDR effects of these drugs in ATC cells. Methods CAL62 and 8505C cell were treated with adriamycin (Adr), docetaxel (Doce), and THC (Cur) at IC ₅₀ and half IC ₅₀ dozes. Wound healing assay, spheroid formation in soft agar, apoptosis and oxidative stress were analyzed in both cell lines. Multidrug resistancy activity factor (MAF) alterations of three main groups of ABC transporter proteins (MDR1, BCRP, and MRP1/2) were evaluated using flow-cytometry. Results THC was more potent than docetaxel and adriamycin in analyses of cell migration, spheroid formation, antioxidant capacity, and apoptosis induction in both cell lines. ABC transporter activities displayed dynamic alterations based on the cell, the substances used, and the dosages. Adriamycin and docetaxel stimulated MDR activities across all MDR protein groups, whereas THC particularly suppressed MDR1 in both cell lines. As the relative markers of Cancer Stem Cell (CSC) activity, Spheroid formation and BCRP values were reduced by THC. Conclusion Doxorubicin and Adriamycin have anti-cancer properties, but remarkably stimulate MDR activities of ATC cells. THC demonstrates anti-cancer potential comparable to that of doxorubicin and Adriamycin and moreover, it has the potential on suppressing stem cell functions and MDR activities.