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

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 well- differentiated thyroid cancer cell line, NPA. OCT bound to its receptor at the same rate a...

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Bibliographic Details
Published in:ENDOCRINE JOURNAL 1999, Vol.46(2), pp.243-252
Main Authors: OKANO, KUNIHIKO, USA, TOSHIRO, OHTSURU, AURA, TSUKAZAKI, TOMOO, MIYAZAKI, YOUICHI, YONEKURA, AKIHIKO, NAMBA, HIROYUKI, SHINDOH, HIROYUKI, YAMASHITA, SHUNICHI
Format: Article
Language:eng ; jpn
Subjects:
22-oxa-1,25-dihydroxyvitamin D3(OCT)
Animals
Antineoplastic Agents - pharmacology
Blotting, Northern
c-myc gene
Calcitriol - analogs & derivatives
Calcitriol - pharmacology
Carcinoma, Papillary - genetics
Carcinoma, Papillary - metabolism
Carcinoma, Papillary - pathology
Cell Count - drug effects
Cell Division - drug effects
Cell Survival - drug effects
DNA - biosynthesis
Genes, myc
Hormone therapy
Humans
Mice
Mice, Nude
Receptors, Calcitriol - metabolism
Thyroid cancer cell
Thyroid Neoplasms - genetics
Thyroid Neoplasms - metabolism
Thyroid Neoplasms - pathology
Transfection
Tumor Cells, Cultured
Vitamin D3
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Summary: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 well- differentiated 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(OH2)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.
ISSN:0918-8959
1348-4540
DOI:10.1507/endocrj.46.243