Melatonin slowed the early biochemical progression of hormone‐refractory prostate cancer in a patient whose prostate tumor tissue expressed MT₁ receptor subtype

Abstract

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.

Therapeutic Actions of Melatonin in Cancer: Possible Mechanisms

“…Both melatonin and its analog 2-iodomelatonin attenuate epidermal growth facto (EGF)-stimulated cyclin D1 levels and cell proliferation in human LNCaP prostate cancer cells. 97 Melatonin had no effect on androgen-insensitive prostate cancer cell proliferation (DU145 and PC-3 cells) in which the MT 1 receptor mediated signal transduction was defective. 98 Melatonin inhibited the proliferation of hormone-dependent LNCaP prostate cancer cells partly through MT 1 receptor activation both in vitro and in vivo as shown in the nude mice xenograft model.…”

“…Based on serum PSA measurements, it was shown that administration of melatonin (5 mg/day at 20:00 hours) induced stabilization of prostate cancer disease, thus suggesting that melatonin had oncostatic action in prostate cancer patients. 97 Melatonin has been shown to reduce prostate cancer cell number and stop cell cycle progression in both androgendependent LNCaP cells and androgen independent PC3 cells. These effects were not mediated by membrane melatonin receptors and did not involve protein kinase A (PKA) activation.…”

“…98 Melatonin inhibited the proliferation of hormone-dependent LNCaP prostate cancer cells partly through MT 1 receptor activation both in vitro and in vivo as shown in the nude mice xenograft model. 97 The effect of melatonin on melatonin receptor expression and levels of prostate serum antigen (PSA) was evaluated in prostate cancer patients by examining cancer tissue biopsy and blood serum. MT 1 melatonin receptors were expressed in prostate tumors.…”

Melatonin secretion rhythm and G protein mutations of patients with ovarian and breast cancer

“…It has been shown that there are probable relationships between the tumor development and melatonin [10,11]. The suppression of pineal function plays role in the etiology of several cancer types [12][13][14]. Lissoni et al [18] divided into two groups the patients and they administrated melatonin (20 milligrams per day) every day besides chemotherapy to one group and they administrated only chemotherapy to other group in a study that they conducted including totally two hundred fifty (250) patients with metastatic tumor consisting of one hundred four (104) patients with gastric carcinoma, seventy seven (77) patients with breast carcinoma, forty two (42) patients with gastrointestinal carcinoma and twenty seven (27) patients with tumors belonging to head and neck region.…”

“…The fact that there is a probable relationship between the tumor development and the products released by the pineal gland has been shown in many various studies [9][10][11]. It has been detected that the suppression of the function of the pineal gland plays role in the etiology of the breast cancer, that of ovary cancer, that of prostate cancer and that of malign melanoma [12][13][14]. Many studies concerning pineal and immune function disorders in patients with cancer have been conducted and, it has been stated that the reduction in the serum melatonin level may be a clue for the malignancy [15].…”