IC50: 5.5–10 μM

Transforming growth factor-β (TGF-β) is a growth factor which is capable of inhibiting prostate cell growth in vitro, and has apparent prostate cell growth regulatory roles in vivo. A second element of potential importance in regulating the growth of prostate cancer cells is the serine/threonine kinase, protein kinase C (PKC). PKC is a signaling enzyme of known importance in regulating the growth and/or differentiation of a variety of cell types; inhibition of its kinase activity is associated with loss of regulatory function. Tamoxifen is a drug known to have TGF-β modulatory and PKC inhibitory effects.

In vitro: IC50s for growth inhibition ranged from 5.5–10 μM, and were not affected by estrogen. Tamoxifen-mediated growth inhibition was not associated with induction of TGF-β. However, tamoxifen treatment was associated with inhibition of PKC, which was followed by induction of p21waf1/cip1, Rb dephosphorylation, and G1/S phase cell cycle arrest [1].

In vivo: The tumor cell kinetics of MCF-7 human breast carcinoma xenografts grown in nude mice can be significantly altered by hormonal manipu lation. Tamoxifen treatment or E2 deprivation resulted in an approximate doubling of the Tpol and an approximately 40% reduction in labeling index as compared to E2-stimulated tumors. An increase in cell loss rate was calculated for both tamoxifen treatment and E2 deprivation [2].

Clinical trial: Tamoxifen reduces the risk of recurrence and death from breast cancer when given as adjuvant therapy, and it provides effective palliation for metastatic breast cancer. Its use is therefore indicated for both premenopausal and postmenopausal women having estrogen-receptor–positive invasive breast cancer [3].

References:
[1] Rohlff C, Blagosklonny MV, Kyle E, Kesari A, Kim IY, Zelner DJ, Hakim F, Trepel J, Bergan RC.? Prostate cancer cell growth inhibition by tamoxifen is associated with inhibition of protein kinase C and induction of p21(waf1/cip1). Prostate. 1998 Sep 15;37(1):51-9.
[2] Jann N.? Sarkaria, David F. C. Gibson, V. Craig Jordan, John F. Fowler, Mary J. Lindstrom, and
R.? Timothy Mulcahy. Tamoxifen-induced Increase in the Potential Doubling Time of MCF-7 Xenografts as Determined by Bromodeoxyuridine Labeling and Flow Cytometry. CANCER RESEARCH 5.1. 4413-1417, September 15, 1993.
[3] Osborne CK.? Tamoxifen in the treatment of breast cancer. N Engl J Med. 1998 Nov 26;339(22):1609-18.