Inhibition of androgen-sensitive LNCaP prostate cancer growth in vivo by melatonin: Association of antiproliferative action of the pineal hormone with mt1 receptor protein expression

Abstract

BACKGROUND. Potential involvement of the mt1 receptor in the antiproliferative action of melatonin on androgen-sensitive LNCaP cells, and melatonin-induced modulation of androgen-insensitive PC-3 cell growth, have been reported in vitro. The effects of melatonin on prostate cancer cell proliferation and their association with mt1 receptor expression were investigated in athymic nude mice xenograft models of LNCaP and PC-3 cells. METHODS. Daily saline or melatonin (4 μg/g body weight) was given to nude mice before or after tumor cell inoculation. Tumor volume was measured periodically, and expression of PCNA, cyclin A, PSA, and mt1 receptor was assessed by immunohisto(cyto)chemistry and/or Western blotting. RESULTS. Melatonin inhibited the growth of LNCaP tumors, without affecting the growth of PC-3 xenografts, in nude mice. It induced significant decreases in the expression of PCNA, cyclin A, and PSA in LNCaP tumors. Expression of mt1 receptor protein was demonstrated in LNCaP cells, but not in PC-3 cells, both in vivo and in vitro. CONCLUSIONS. The antiproliferative action of melatonin on LNCaP tumor growth was demonstrated in vivo, and its association with mt1 receptor protein expression suggests the potential involvement of the receptor in the antitumor activity of the pineal gland hormone. © 2001 Wiley-Liss, Inc.