Melatonin and prostate cancer cell proliferation : interplay with castration, epidermal growth factor and androgen sensitivity

by Siu, Wing-fai

(Uncorrected OCR) Abstract of thesis entitled

Melatonin and Prostate Cancer CellProlifenltion:

Interplay with Castration, [~pidermal (;row'thFactor and Androgen Sensitivity

submitted by

Sill Wing F~li

for the degree of Master of Philosophy at T'he University of [long Kong

in December 2001

Melatonin (MLT). a putative oncostatic molecule, is secreted predominantly by the pineal gland. Recent studies have reported antiproliJerative actions of melatonin on androgen-sensitive LNCaP prostate cancer growth in vitro and in vivo, as well as a potential modulatory effect of melatonin on androgen-insensitive PC-3 and DU 145 prostate cancer cell proli feration in vitro. In this thesis, the eJlects of combined melatonin and castration on LNCaP tumor growth, potential interactions between melatonin and epidermal growth factor (E~GF) on LNeal) cell proliferation, and melatonin actions on the proliferation of DU 145 and PC-3 cells were determined.

To investigate the in VIVO action of melatonin on androgen-sensitive prostate tumor growth under androgen-depri vcd condition, castrated male athymic nude mice inoculated with LNCaP prostate cancer cells were given daily melatonin (4 ~lg/g body weight) or saline treatment. While loss of androgenic stimulation through castration induced decreases in the incidence and growth of LNCaP prostate tumor, fllrther decreases in LNCaP tumor incidence and growth were noted in castrated mice which also received melatonin. Furthermore, MT'! receptor, EGF and EGFR were expressed in the malignant cells of the same human prostate cancer tissue by immunohistochemistry. EGF-induced increase in CH]thymidine incorporation into LNCaP cells was attenuated by melatonin or 2-iodomclatonin (a melatonin receptor agonist). This modulatory effect of melatonin or 2-iodomelatonin was associated with reduced cyclin D 1 levels in LNCaP cells.