Anti-proliferative effects of a novel isoflavone derivative in medullary ...

Y. Greenman et al. / Journal of Steroid Biochemistry & Molecular Biology 132 (2012) 256– 261 261
inhibition of proliferation was achieved through pathways leading
to both apoptosis and necrosis, while in WRO and ARO cell
lines, cell death occurred through apoptosis only [26]. Clearly further
work is needed to dissect the pathways through which this
novel compound exerts its antitumoral effects.
In conclusion, our results suggest that estrogens are involved
in proliferation of the human MTC cell line TT, and that this property
can be utilized to design promising anti-cancer drugs for the
management of medullary thyroid carcinoma.
Conflict of interest
All authors declare that there are no actual or potential conflicts
of interest, including financial, personal or other relationships
with other people or organizations that could have inappropriately
influenced this work.
Role of the funding source
This work did not receive financial support by any specific sponsor
or grant.
References
[1] A. Machens, S. Hauptmann, H. Dralle, Disparities between male and female
patients with thyroid cancers: sex differences or gender divide? Clinical
Endocrinology 65 (2006) 500–505.
[2] I. Dos Santos Silva, A.J. Swerdlow, Sex differences in the risks of hormonedependent
cancers, American Journal of Epidemiology 138 (1993) 10–28.
[3] H. Inoue, K. Oshimo, H. Miki, M. Kawano, Y. Monden, Immunohistochemical
study of estrogen receptors and the responsiveness to estrogen in papillary
thyroid carcinoma, Cancer 72 (1993) 1364–1368.
[4] C. Egawa, Y. Miyoshi, K. Iwao, E. Shiba, S. Noguchi, Quantitative analysis of
estrogen receptor-alpha and -beta messenger RNA expression in normal and
malignant thyroid tissues by real-time polymerase chain reaction, Oncology 61
(2001) 293–298.
[5] D. Manole, B. Schildknecht, B. Gosnell, E. Adams, M. Derwahl, Estrogen
promotes growth of human thyroid tumor cells by different molecular mechanisms,
Journal of Clinical Endocrinology and Metabolism 89 (2001) 1072–1077.
[6] S. Rajoria, R. Suriano, A. Shanmugam, Y.L. Wilson, S.P. Schantz, J. Geliebter, R.K.
Tiwari, Metastatic phenotype is regulated by estrogen in thyroid cells, Thyroid
20 (2010) 33–41.
[7] S. Guyetant, M.C. Rousselet, M. Durigon, D. Chappard, B. Franc, O. Guerin, J.P.
Saint-Andre, Sex-related C cell hyperplasia in the normal human thyroid: a
quantitative autopsy study, Journal of Clinical Endocrinology and Metabolism
82 (1997) 42–47.
[8] M. d’Herbomez, P. Caron, C. Bauters, C.D. Cao, J.L. Schlienger, R. Sapin, L. Baldet,
B. Carnaille, J.L. Wémeau, French Group GTE (Groupe des Tumeurs Endocrines):
reference range of serum calcitonin levels in humans: influence of calcitonin
assays, sex, age, and cigarette smoking, European Journal of Endocrinology/European
Federation of Endocrine Societies 157 (2007) 749–755.
[9] A. Machens, F. Hoffman, C. Sekulla, H. Dralle, Importance of gender-specific
calcitonin thresholds in screening for occult sporadic medullary thyroid cancer,
Endocrine Related Cancer 16 (2009) 1291–1298.
[10] E. Kebebew, P.H. Ituarte, A.E. Siperstein, Q.Y. Duh, O.H. Clark, Medullary thyroid
carcinoma: clinical characteristics, treatment, prognostic factors, and a
comparison of staging systems, Cancer 88 (2000) 1139–1148.
[11] E. Modigliani, R. Cohen, J.M. Campos, B. Conte-Devolx, B. Maes, A. Boneu, M.
Schlumberger, J.C. Bigorgne, P. Dumontier, L. Leclerc, B. Corcuff, I. Guilhem, the
GETC Study Group, Prognostic factors for survival and for biochemical cure in
medullary thyroid carcinoma: results in 899 patients, Clinical Endocrinology
48 (1998) 265–273.
[12] S. Schröder, W. Böcker, H. Baisch, C.G. Bürk, H. Arps, I. Meiners, H. Kastendieck,
P.U. Heitz, Klöppel, Prognostic factors in medullary thyroid carcinomas. Survival
in relation to age, sex, stage, histology, immunocytochemistry, and DNA
content, Cancer 61 (1988) 806–816.
[13] N. Bhattacharyya, A population-based analysis of survival factors in differentiated
and medullary thyroid carcinoma, Otolaryngology-Head and Neck Surgery
128 (2003) 115–123.
[14] S. Roman, R. Lin, J.A. Sosa, Prognosis of medullary thyroid carcinoma: demographic,
clinical and pathological predictors of survival in 1252 cases, Cancer
107 (2006) 2134–2142.
[15] American Thyroid Association Guidelines Task ForceR.T. Kloos, C. Eng, D.B.
Evans, G.L. Francis, R.F. Gagel, H. Gharib, J.F. Moley, F. Pacini, M.D. Ringel, M.
Schlumberger, S.A. Wells Jr., Medullary thyroid cancer: management guidelines
of the American Thyroid Association, Thyroid 19 (2009) 565–612.
[16] M. Cakir, A.B. Grossman, Medullary thyroid cancer: molecular biology and novel
molecular therapies, Neuroendocrinology 90 (2009) 323–348.
[17] F. Kohen, B. Gayer, T. Kulik, V. Frydman, N. Nevo, S. Katzburg, R. Limor, O. Sharon,
N. Stern, D. Somjen, Synthesis and evaluation of the antiproliferative activities
of derivatives of carboxyalkyl isoflavones linked to N-t-Boc-hexylenediamine,
Journal of Medicinal Chemistry 50 (2007) 6405–6410.
[18] G.A. Williams, S.C. Kukreja, E.N. Bowser, G.K. Hargis, C.P. Greenberg, W.J. Henderson,
Prolonged effect of estradiol on calcitonin secretion, Bone and Mineral
1 (1986) 415–420.
[19] T. Naveh-many, G. Almogi, N. Livni, J. Silver, Estrogen receptors and biologic
response in rat parathyroid tissue and C cells, Journal of Clinical Investigation
90 (1992) 2434–2438.
[20] M.I. Whitehead, G. Lane, P.T. Townsend, G. Abeyasekera, C.J. Hillyard, J.C.
Stevenson, Effects in postmenopausal women of natural and synthetic estrogens
on calcitonin and calcium-regulating hormone secretion. Relevance to
postmenopausal osteoporosis, Acta Obstetricia et Gynecologica Scandinavica
Supplement 106 (1981) 27–32.
[21] A.H. Taylor, F. Al-Azzawi, Immunolocalisation of oestrogen receptor
beta in human tissues, Journal of Molecular Endocrinology 24 (2000)
145–155.
[22] C. Bléchet, P. Lecomte, L. De Calan, P. Beutter, S.S. Guyétant, Expression of sex
steroid hormone receptors in C cell hyperplasia and medullary thyroid carcinoma,
Virchows Archiv 450 (2007) 433–439.
[23] A.M. Cho, M.K. Lee, K.H. Nam, W.Y. Chung, C.S. Park, J.H. Lee, T. Noh, W.I. Yang,
Y. Rhee, S.K. Lim, H.C. Lee, E.J. Lee, Expression and role of estrogen receptor
a and b in medullary thyroid carcinoma: different roles in cancer growth and
apoptosis, Journal of Endocrinology 195 (2007) 255–263.
[24] K. Yang, C.E. Pearson, N.A. Samaan, Estrogen receptor and hormone responsiveness
of medullary thyroid carcinoma cells in continuous culture, Cancer
Research 48 (1988) 2760–2763.
[25] G.G.J.M. Kuiper, J.G. Lemmen, B. Carlsson, J.C. Corton, S.H. Safe, P.T. van der Saag,
B. van der Burg, J.Å. Gustafsson, Interaction of estrogenic chemicals and phytoestrogens
with estrogen receptor �, Endocrinology 139 (1998) 4252–4263.
[26] D. Somjen, M. Grafi-Cohen, S. Katzburg, G. Weisinger, E. Izkhakov, N. Nevo,
O. Sharon, Z. Kraiem, F. Kohen, N. Stern, Anti-thyroid cancer properties of a
novel isoflavone derivative 7-(O)-carboxymethyl daidzein conjugated to N-t-
Boc-hexylenediamine in vitro and in vivo, Journal of Steroid Biochemistry and
Molecular Biology 126 (2011) 95–103.