Xanthohumol stimulates iodide uptake in rat thyroid-derived FRTL-5 cells.
Sodium-iodide-symporter (NIS), an integral plasma membrane glycoprotein, mediates the sodium-dependent active uptake of iodide (I(-)) into the thyroid gland, which is a fundamental step in thyroid hormone synthesis. In this work, we analyzed the influence of xanthohumol (XN), a prenylated chalcone from hops (Humulus lupulus L.), on the I(-) uptake in a cell culture model of normal, nontransformed rat thyrocytes (FRTL-5). Acute treatment with nanomolar concentrations of XN does not influence I(-) uptake, but after 2 and 3-days of XN stimulation an increase in I(-) uptake was observed; I(-) uptake was maximally increased by 50% compared to control after 3-days of XN stimulation at 1 nM. A clear time-dependent stimulation was observed which showed no marked concentration relationship, however. To investigate whether expression of NIS mRNA is also increased, we grew FRTL-5 cells for 3-days in a medium containing increasing concentrations of XN (0.1 nM-1 muM). Northern blot analysis showed no difference in NIS mRNA transcript levels between control cells and those treated with different concentrations of XN. This study revealed that nanomolar concentrations of XN, a unique compound with anticancer properties, exert stimulating effects on radioiodide uptake. In contrast to many other plant-derived phenolic secondary metabolites such as (iso-)flavonoids, which inhibit I(-) uptake, XN might be an interesting candidate for more efficient radioiodide therapy of thyroid and perhaps other cancer expressing NIS such as breast cancer.
Radović
Branislav
B
Institut für Experimentelle Endokrinologie und Endokrinologisches, Forschungszentrum EnForCé, Charité Universitätsmedizin Berlin, Berlin, Germany. branislav.radovic@charite.de
Schmutzler
Cornelia
C
Köhrle
Josef
J
D000818:Animals; D015152:Blotting, Northern; D002460:Cell Line; D005419:Flavonoids; D015870:Gene Expression / Q000187:drug effects; D027582:Humulus / Q000737:chemistry; D007454:Iodides / Q000378:metabolism*; D007457:Iodine Radioisotopes; D011427:Propiophenones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D027981:Symporters / Q000235:genetics; D013961:Thyroid Gland / Q000187:drug effects* / Q000378:metabolism*; D000099209:Sodium-Iodide Symporters
D005419:Flavonoids; D007454:Iodides; D007457:Iodine Radioisotopes; D011427:Propiophenones; D012333:RNA, Messenger; D027981:Symporters; D000099209:Sodium-Iodide Symporters; C104536:xanthohumol