Growth inhibition of human thyroid carcinoma and goiter cells in vitro by the isoflavone derivative 7-(O)-carboxymethyl daidzein conjugated to N-t-boc-hexylenediamine.
BACKGROUND
Estrogens may enhance thyroid cancer cell growth. We have recently reported that a novel isoflavone-derived anti-estrogenic compound developed in our laboratory, the N-t-boc-hexylenediamine derivative of 7-(O)-carboxymethyl daidzein (cD-tboc), can induce apoptosis and retard growth in human thyroid carcinoma cell lines through inhibitory interaction on estrogen receptor β. Here we tested the hypothesis that cD-tboc can likewise retard cell growth in cultured human thyroid papillary carcinoma cells, normal thyroid cells, and goiter cells removed during thyroidectomy.


METHODS
In vitro experiments in cultured human thyroid normal, goiter, and papillary thyroid carcinoma (PTC) cells were performed. Estrogen receptors α and β (ERα and ERβ), DNA synthesis and creatine kinase (a marker of estrogenic genomic response), and the effects of cD-tboc on DNA synthesis in cultured human PTC cells were assessed.


RESULTS
First, all cell types thus harvested and grown in culture expressed both ERα and ERβ, with a variably higher abundance of ERβ over ERα seen in the goiter and PTC cells, but not in the normal thyroid cells. Second, DNA synthesis and creatine kinase were increased in response to estradiol-17β (E2), the ERα agonist propyl-pyrazole-trisphenol as well as the ERβ agonist diarylpropionitrile. Third, cD-tboc dose-dependently inhibited DNA synthesis in cultured human PTC cells (-65%) and to a lesser extent in goiter cells (∼-30%).


CONCLUSIONS
This study provides the first evidence that cD-tboc can act to inhibit growth in primary cultures of human PTC cells and goiter cells removed during thyroidectomy. Whether this can be utilized for the treatment of human thyroid cancer and/or goiter remains to be explored.
Institute of Endocrinology, Metabolism, and Hypertension, Tel Aviv University, Tel Aviv, Israel.
Dalia
D
Somjen
Meital
M
Grafi-Cohen
Gary
G
Weisinger
Elena
E
Izkhakov
Orli
O
Sharon
Zaki
Z
Kraiem
Dan
D
Fliss
Daniel
D
Zikk
Fortune
F
Kohen
Naftali
N
Stern
D002277:Carcinoma / Q000188:drug therapy*; D002291:Carcinoma, Papillary; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000096:biosynthesis / Q000187:drug effects; D047629:Estrogen Receptor beta / Q000096:biosynthesis* / Q000187:drug effects; D006042:Goiter / Q000473:pathology; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology / Q000627:therapeutic use*; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000473:pathology; D013964:Thyroid Neoplasms / Q000188:drug therapy*
C576978:7-(O)-carboxymethyl daidzein N-t-Boc-hexylenediamine conjugate; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D007529:Isoflavones; D004958:Estradiol