Effect of 22-Oxa-1,25-Dihydroxyvitamin D3 on Human Thyroid Cancer Cell Growth.

Abstract

Abstract.To examine whether synthetic vitamin D3 analog, 22-oxa-1,25(OH)2D3 (OCT) has an inhibitory effect on the growth of thyroid carcinoma, we tested the in vitro and in vivo effects of OCT on the growth of a welldifferentiated thyroid cancer cell line, NPA. OCT bound to its receptor at the same rate as 1,25(OH)2D3, and inhibited the proliferation of NPA cells in vitro in a dose-dependent manner, similar to that observed with 1,25(OH)2D3. Northern blot analysis showed that steady-state and fetal bovine serum-stimulated levels of c-myc mRNA were suppressed after 0.5-4 hour treatment with OCT. Transfection studies with the deletion mutants of the 5"-up-stream flanking region of c-myc/chroramphenicol acetyltransferase chimera genes indicated the presence of an OCT responsive element between -410 and -106. Next, we examined OCT effects in implanted NPA tumor cells in nude mice. OCT showed no remarkable hypercalcemic effect compared to 1, 25 (0H2)D3, but OCT and 1, 25 (OH2)D3, had no significant inhibitory effect in vivo after either intra-tumor or intra-peritoneum injection. Our results demonstrate that OCT inhibits the proliferation of well-differentiated thyroid cancer in an in vitro system associated with the suppression of c-myc mRNA, but this inhibitory effect was not reproducible in in vivo model.

Mechanisms implicated in the growth regulatory effects of vitamin D in breast cancer.

“…(Mathiasen et al 1993). The observation that 1,25(OH) 2 D 3 is able to regulate c-myc at the mRNA level is in accordance with the finding of a putative VDRE which has been reported in the human c-myc gene (Okano et al 1999).…”

Body Mass Index in the Evaluation of Thyroid Cancer Risk

“…This hormone, in addition to its role in calcium homeostasis, has been recognized to play a role in the modulation of the proliferation and differentiation of several cell types (32). In vitro studies have demonstrated that vitamin D inhibits the proliferation of well-differentiated thyroid cancer cells in a dose-dependent manner (32,33). Therefore, as vitamin D is known to be protective in terms of cancer, insufficient levels of this hormone might be contributing to an increased cancer risk in individuals with excess weight.…”

Vitamin D3 Treatment for Locally Advanced Thyroid Cancer: A Case Report

“…In terms of thyroid cancer, there have been several reports on the efficacy of vitamin D3 to inhibit proliferation and to induce re-differentiation of thyroid cancer cell lines in vitro [5,6]. Recently, similar results have also been reported in animal models and thus clinical trials are anticipated for further investigation on the therapeutic role of vitamin D3 in thyroid cancer [7].…”

“…In addition, vitamin D3 has been shown to inhibit the proliferation of various thyroid cancer cell lines in vitro [5,6]. Recently, Dackiw et al reported that calcitriol administration reduced the tumor burden and inhibited metastatic growth in an animal model of thyroid cancer [7].…”