Melatonin inhibited the proliferation of
hormone-independent LNCaP
prostate cancer cells partly via
MT1 receptor activation both in vitro and in nude mice xenograft model. In this study, the
melatonin receptor expression in the
prostate cancer tissue of a patient with bone
metastases and the effect of
melatonin on the biochemical progression of
hormone-refractory prostate
tumor which later developed in the same patient were reported. Saturation and competition 2-[125I]iodomelatonin binding assays were conducted on prostate
tumor tissue obtained by transurethral resection of the prostate from the index patient. The receptor subtype identity of
melatonin receptor expressed in the
cancer tissue was determined by comparison of the rank order of inhibition constants (Ki) of various melatonergic
ligands and the affinity of
4-phenyl-2-propionamidotetraline relative to
melatonin in inhibiting 2-[125I]iodomelatonin binding to the
tumor sample and to human cell lines stably transfected with MT1 or
MT2 melatonin receptor subtype.
MT1 receptor expression in the
cancer tissue was also examined by immunohistochemistry. The surgically castrated patient later developed biochemical relapse of his disease. His serum total
prostate-specific antigen (PSA) level was monitored before and during treatment with 5 mg/day oral
melatonin at 20:00 hr. High-affinity (Kd = 103.7 pm)
MT1 melatonin receptor subtype was expressed by the patient's
prostate cancer. As indicated by his PSA levels,
melatonin induced stabilization of his
hormone-refractory disease for 6 wk. This report validates
melatonin's oncostatic action on
prostate cancer and the potential involvement of
MT1 receptor subtype in the attendant antiproliferative signal transduction as suggested by recent preclinical laboratory findings in a human.