New study below. 
While there are a good number of PCa studies that report on the effects of disturbing the circadian rhythm, few look at the therapeutic use of melatonin.
The study confirms its anti-androgen effects - the androgen receptor was excluded from the nucleus of the cell. (Translocation of AR to the nucleus is necessary for its activities.)
"IGFBP3 and IGF1R were up- and downregulated, respectively"
IGF is the insulin-like growth factor, & there is extensive literature on the role of IGF-I in PCa profression.
IGFBP3 is the main IGF binding protein. It is down-regulated in PCa, which results in higher levels of free (bioavailable) IGF-I. Restoring IGFBP3 lowers available IGF-I.
IGF1R is the receptor for IGF-I, & it's good to see it downregulated.
(I doubt that many PCa professionals subscribe to the Journal of Pineal Research.)
J Pineal Res. 2016 Oct 13. doi: 10.1111/jpi.12373. [Epub ahead of print]
IGFBP3 and MAPK/ERK signaling mediates melatonin-induced anti-tumor activity in prostate cancer.
Mayo JC1,2, Hevia D3, Quiros-Gonzalez I4, Rodriguez-Garcia A3, Gonzalez-Menendez P3,5, Cepas V3,5, Gonzalez-Pola I3,5, Sainz RM3,5.
1Departamento de Morfología y Biología Celular. University of Oviedo, Julián Clavería 6, 330006, Oviedo, Spain. email@example.com.
2Redox Biology Unit. The University Institute of Oncology of Asturias (IUOPA). University of Oviedo. firstname.lastname@example.org.
3Departamento de Morfología y Biología Celular. University of Oviedo, Julián Clavería 6, 330006, Oviedo, Spain.
4Department of Physics, Cambridge Research UK, University of Cambridge.
5Redox Biology Unit. The University Institute of Oncology of Asturias (IUOPA). University of Oviedo.
Treatment of prostate cancer (PCa), a leading cause of cancer among males lacks successful strategies especially in advanced, hormone-refractory stages. Some clinical studies have shown an increase in neuroendocrine like cells parallel to the tumor progression but their exact role is a matter of debate. The prostate is a well-known target for melatonin, which reduces PCa cells proliferation and induces neuroendocrine differentiation. To evaluate the mechanisms underlying the indole effects on neuroendocrine differentiation and its impact on PCa progression, we used a cell culture model (LNCaP) and a murine model (TRAMP). Persistent ERK1/2 activation was found in both, melatonin and androgen-deprived cells. Melatonin blocked nuclear translocation of androgen receptor (AR), thus confirming anti-androgenic actions of the indole. However, by using a comparative genome microarray to check the differentially expressed genes in control, melatonin or androgen-deprived cells, some differences were found, suggesting a more complex role of the indole. By comparing control cells with those treated with melatonin or depleted of androgen, a cluster of 26 differentially expressed genes (± 2.5-fold) was found. Kallikreins (KLK)2 and KLK3 (PSA) were dramatically downregulated by both treatments whereas IGFBP3 and IGF1R were up- and downregulated, respectively, in both experimental groups, thus showing a role for IGF in both scenarios. Finally, melatonin prolonged the survival of TRAMP mice by 33% when given at the beginning or at advances stages of the tumor. Serum IGFBP3 was significantly elevated by the indole in early stages of the tumor, confirming in vivo the role of the IGF signaling in the oncostatic action of the indole. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
IGFBP3; TRAMP mice; androgen signaling; melatonin; prostate cancer
PMID: 27736013 DOI: 10.1111/jpi.12373
[PubMed - as supplied by publisher]