Antiproliferative effects of melatonin on the growth of rat pituitary prolactin-secreting tumor cells in vitro.
Earlier studies showed that melatonin reduced the growth of 17-beta-estradiol (E(2))-induced rat pituitary prolactin-secreting tumor (prolactinoma) in vivo. The mechanisms of melatonin's inhibitory action on the prolactin-secreting tumor were further explored by investigating the in vitro effects of melatonin on the growth of pituitary prolactin-secreting tumor cells. Primary cultured prolactinoma cells from E(2)-induced rat pituitary prolactin-secreting tumor were treated with 10(-5), 10(-4) or 10(-3) m melatonin for 5 days. Apoptosis was evaluated using flow cytometry and the TdT-mediated dUTP nick-end labeling (TUNEL) method. In addition, cell viability was analyzed by (3,4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. It was found that incubation of prolactinoma cells with 10(-5), 10(-4) or 10(-3) m melatonin for 5 days inhibited cell growth and increased cell apoptosis. Furthermore, melatonin increased caspase-3 activity, Bax mRNA expression, and cytochrome c protein expression. Conversely, Bcl-2 mRNA expression and mitochondrial membrane potential were inhibited by melatonin treatment. Our results further suggest that melatonin inhibits tumor growth by inducing apoptosis of rat pituitary prolactin-secreting tumor directly via the damage of mitochondria.
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; D049109:Cell Proliferation; D006131:Growth Inhibitors / Q000502:physiology*; D008297:Male; D008550:Melatonin / Q000502:physiology*; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured
D006131:Growth Inhibitors; D011388:Prolactin; D008550:Melatonin