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Antiproliferative effects of melatonin on the growth of rat pituitary prolactin‐secreting tumor cells in vitro
Author(s) -
Yang QuanHui,
Xu JianNing,
Xu RongKun,
Pang ShiuFun
Publication year - 2007
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2006.00403.x
Subject(s) - melatonin , prolactin , medicine , apoptosis , endocrinology , prolactinoma , pinealocyte , pituitary tumors , biology , prolactin cell , tunel assay , viability assay , cell growth , pineal gland , pituitary neoplasm , pituitary gland , hormone , biochemistry
Earlier studies showed that melatonin reduced the growth of 17‐ β ‐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.