Abstract
Others and our previous studies showed that the increase of IGF-1 was involved in the formation of goiter. Our aim here was to evaluate the possible effects of diosgenin on cell proliferation induced by IGF-1 in primary human thyroid cells. The cells were treated with or without different concentrations of diosgenin in the present or absent of IGF-1 for 24, 48 and 72 h, respectively. Cell viability was determined by MTT, and cell proliferation was tested by EdU assay, and cell cycle analysis was performed by FACS. In addition, Cyclin D1 and B1 protein expression was tested by Western Blotting, respectively. We found that IGF-1 promoted cell cycle progression to S phase and increased the primary human thyroid cells proliferation. Diosgenin decreased the protein expression of cyclin D1 and resulted in cell G0/G1 arrest. Importantly, when the human thyrocytes were exposed to diosgenin in the present of IGF-1, the IGF-1 inducing proliferation was significantly decreased and the proportion of the cells in G0/G1 phase was increased, while that of S phase was decreased. This study shows that diosgenin inhibited cell proliferation, caused G0/G1 arrest, and could inhibit cell proliferation induced by IGF-1 in primary human thyroid cells.
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Ambesi-Impiombato, F. S., Parks, L. A., and Coon, H. G., Culture of hormone-dependent functional epithelial cells from rat thyroids. Proc. Natl. Acad. Sci. U. S. A., 77, 3455–3459 (1980).
Baldin, V., Lukas, J., Marcote, M. J., Pagano, M., and Draetta, G., Cyclin D1 is nuclear protein required for cell cycle progression in G1. Genes Dev., 7, 812–821 (1993).
Beier, F., Lee, R. J., Taylor, A. C., Pestell, R. G., and Luvalle, P., Identification of the cyclin D1 gene as a target of activating transcription factor 2 in chondrocytes. Proc. Natl. Acad. Sci. U. S. A., 96, 1433–1438 (1999).
Bertrand, F., Philippe, C., Antoine, P. J., Baud, L., Groyer, A., Capeau, J., and Cherqui, G., Insulin activates nuclear factor kappa B in mammalian cells through a Raf-1-mediated pathway. J. Biol. Chem., 270, 24435–24441 (1995).
Breous, E., Wenzel, A., and Loos, U., Graves’ IgG activate upstream enhancer of the sodium/iodide symporter. Mol. Cell. Endocrinol., 213, 109–113 (2003).
Caraccio, N., Cuccato, S., Pratesi, F., Dardano, A., Ursino, S., Chimenti, D., Boldrini, L., Materazzi, G., Migliorini, P., and Monzani, F., Effect of type I interferon(s) on cell viability and apoptosis in primary human thyrocyte cultures. Thyroid, 19, 149–155 (2009).
Chiang, C. T., Way, T. D., Tsai, S. J., and Lin, J. K., Diosgenin, a naturally occurring steroid, suppresses fatty acid synthase expression in HER2-overexpressing breast cancer cells through modulating Akt, mTOR and JNK phosphorylation. FEBS Lett., 581, 5735–5742 (2007).
Corbiere, C., Liagre, B., Bianchi, A., Bordji, K., Dauça, M., Netter, P., and Beneytout, J. L., Different contribution of apoptosis to the antiproliferative effects of diosgenin and other plant steroids, hecogenin and tigogenin, on human 1547 osteosarcoma cells. Int. J. Oncol., 22, 899–905 (2003).
Corbière, C., Battu, S., Liagre, B., Cardot, P. J. P., and Beneytout, J. L., SdFFF monitoring of cellular apoptosis induction by diosgenin and different inducers in the human 1547 osteosarcoma cell line. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 808, 255–262 (2004).
Eric, H., Final report of the amended safety assessment of Dioscorea Villosa (Wild Yam) root extract. Int. J. Toxicol., 23Suppl 2, 49–54 (2004).
Heck, S., Lezoualc’h, F., Engert, S., and Behl, C., Insulin-like growth factor-1-mediated neuroprotection against oxidative stress is associated with activation of nuclear factor kappaB. J. Biol. Chem., 274, 9828–9835 (1999).
Heichman, K. A. and Roberts, J. M., Rules to replicate by. Cell, 79, 557–562 (1994).
Innocente, S. A., Abrahamson, J. L., Cogswell, J. P., and Lee, J. M., p53 regulates a G2 checkpoint through cyclin B1. Proc. Natl. Acad. Sci. U. S. A., 96, 2147–2152 (1999).
Jiang, Y., Cheng, D. W., Levi, E., and Singh, L. P., IGF-1 increases laminin, cyclin D1, and P21Cip1 expression in glomerular mesangial cells: an investigation of the intracellular signaling pathway and cell-cycle progression. J. Cell. Biochem., 98, 208–220 (2006).
Juarez-Oropeza, M. A., Diaz-Zagoya, J. C., and Rabinowitz, J. L., In vivo and in vitro studies of hypocholesterolemic effects of diosgenin in rats. Int. J. Biochem., 19, 679–683 (1987).
Kimura, T., Van Keymeulen, A., Golstein, J., Fusco, A., Dumont, J. E., and Roger, P. P., Regulation of thyroid cell proliferation by TSH and other factors: a critical evaluation of in vitro models. Endocr. Rev., 22, 631–656 (2001).
Kofidis, T., de Bruin, J. L., Yamane, T., Balsam, L. B., Lebl, D. R., Swijnenburg, R. J., Tanaka, M., Weissman, I. L., and Robbins, R. C., Insulin-like growth factor promotes engraftment, differentiation, and functional improvement after transfer of embryonic stem cells for myocardial restoration. Stem Cells, 22, 1239–1245 (2004).
Kwon, C. S., Sohn, H. Y., Kim, S. H., Kim, J. H., Son, K. H., Lee, J. S., Lim, J. K., and Kim, J. S., Anti-obesity effect of Dioscorea nipponica Makino with lipase-inhibitory activity in rodents. Biosci. Biotechnol. Biochem., 67, 1451–1456 (2003).
McAnuff, M. A., Harding, W. W., Omoruyi, F. O., Jacobs, H., Morrison, E. Y., and Asemota, H. N., Hypoglycemic effects of steroidal sapogenins isolated from Jamaican bitter yam, Dioscorea polygonoides. Food Chem. Toxicol., 43, 1667–1672 (2005).
Miyakawa, M., Tsushima, T., Murakami, H., Wakai, K., Isozaki, O., and Takano, K., Increased expression of phosphorylated p70S6 kinase and Akt in papillary thyroid cancer tissues. Endocr. J., 50, 77–83 (2003).
Radcliff, K., Tang, T. B., Lim, J., Zhang, Z., Abedin, M., Demer, L. L., and Tintut, Y., Insulin-like growth factor-I regulates proliferation and osteoblastic differentiation of calcifying vascular cells via extracellular signal-regulated protein kinase and phosphatidylinositol 3-kinase pathways. Circ. Res., 96, 398–400 (2005).
Raju, J., Patlolla, J. M., Swamy, M. V., and Rao, C. V., Diosgenin, a steroid saponin of Trigonella foenum graecum (Fenugreek), inhibits azoxymethane-induced aberrant crypt foci formation in F344 rats and induces apoptosis in HT-29 human colon cancer cells. Cancer Epidemiol. Biomarkers Prev., 13, 1392–1398 (2004).
Ren, M., Zhong, X., Ma, C. Y., Sun, Y., Guan, Q. B., Cui, B., Guo, J., Wang, H., Gao, L., and Zhao, J. J., Insulin-like growth factor-1 promotes cell cycle progression via upregulation of cyclin D1 expression through the phosphatidylinositol 3-kinase/nuclear factor-kappaB signaling pathway in FRTL thyroid cells. Acta Pharmacol. Sin., 30, 113–119 (2009).
Saito, J., Kohn, A. D., Roth, R. A., Noguchi, Y., Tatsumo, I., Hirai, A., Suzuki, K., Kohn, L. D., Saji, M., and Ringel, M. D., Regulation of FRTL-5 thyroid cell growth by phosphatidylinositol (OH) 3 kinase-dependent Akt-mediated signaling. Thyroid, 11, 339–351 (2001).
Shishodia, S. and Aggarwal, B. B., Diosgenin inhibits osteoclastogenesis, invasion, and proliferation through the downregulation of Akt, I kappa B kinase activation and NF-kappa B-regulated gene expression. Oncogene, 25, 1463–1473 (2006).
Son, I. S., Kim, J. H., Sohn, H. Y., Son, K. H., Kim, J. S., and Kwon, C. S., Antioxidative and hypolipidemic effects of diosgenin, a steroidal saponin of yam (Dioscorea spp.), on high-cholesterol fed rats. Biosci. Biotechnol. Biochem., 71, 3063–3071 (2007).
Tada, Y., Kanda, N., Haratake, A., Tobiishi, M., Uchiwa, H., and Watanabe, S., Novel effects of diosgenin on skin aging. Steroid, 74, 504–511 (2009).
Taylor, W. G., Elder, J. L., Chang, P. R., and Richards, K. W., Microdetermination of diosgenin from fenugreek (Trigonella foenum-graecum) seeds. J. Agric. Food Chem., 48, 5206–5210 (2000).
Turchan-Cholewo, J., Liu, Y., Gartner, S., Reid, R., Jie, C., Peng, X., Chen, K. C., Chauhan, A., Haughey, N., Cutler, R., Mattson, M. P., Pardo, C., Conant, K., Sacktor, N., McArthur, J. C., Hauser, K. F., Gairola, C., and Nath, A., Increased vulnerability of ApoE4 neurons to HIV proteins and opiates: protection by diosgenin and L-deprenyl. Neurobiol. Dis., 23, 109–119 (2006).
Xiong, W., Pestell, R. G., Watanabe, G., Li, J., Rosner, M. R., and Hershenson, M. B., Cyclin D1 is required for S phase traversal in bovine tracheal myocytes. Am. J. Physiol., 272(6 Pt 1), L1205–L1210 (1997).
Zhong, X., Zhao, J.-J, Gao, L., Liang, J., and Wang, R.-x., Association of insulin-like growth factor-I and thyroid volumes in patients with Graves’ disease. Journal of Shandong University (Health Sciences), 44, 138–142 (2009).
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Bian, D., Li, Z., Ma, H. et al. Effects of diosgenin on cell proliferation induced by IGF-1 in primary human thyrocytes. Arch. Pharm. Res. 34, 997–1005 (2011). https://doi.org/10.1007/s12272-011-0617-y
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DOI: https://doi.org/10.1007/s12272-011-0617-y