Inhibitory effects of melatonin on the growth of pituitary prolactin-secreting tumor in rats.
The in vivo effects of melatonin on proliferation and apoptosis of 17-beta-estradiol (E2)-induced pituitary prolactin-secreting tumor (prolactinoma) were investigated in rats kept in 12 L/12 D (lights on: 06:00-18:00 hr). As melatonin was shown to induce apoptosis of breast and liver tumor cells, we examined whether melatonin would induce apoptosis of rat pituitary prolactinoma cells. 0.125, 0.25, 0.50 or 1.0 mg melatonin/day/rat was administrated subcutaneously at 17:30-18:00 hr. The weight of prolactinomas was measured. Apoptosis was evaluated using the TdT-mediated dUTP nick-end labeling method. It was found that treatment with 0.25 and 0.50 mg melatonin for 97 days inhibited prolactinoma cell proliferation and increased prolactinoma cell apoptosis. Furthermore, melatonin induced mRNA expression of Bax and cytochrome c protein expression. Conversely, mRNA expression of Bcl-2, and mitochondrial membrane potential were inhibited by melatonin treatment. These results suggest that melatonin inhibits the proliferation and induces apoptosis of rat pituitary prolactin-secreting tumor via perturbation of mitochondria physiology.
Yang
Quan-Hui
QH
Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.
Xu
Jian-Ning
JN
Xu
Rong-Kun
RK
Pang
Shiu-Fun
SF
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004958:Estradiol; D020287:In Situ Nick-End Labeling; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D010911:Pituitary Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D015175:Prolactinoma / Q000178:diet therapy / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000970:Antineoplastic Agents; D004958:Estradiol; D011388:Prolactin; D008550:Melatonin