title: Elevated levels of mitochonrial respiratory complexes activities and ATP production in 17-β-estradiol-induced prolactin-secretory tumor cells in male rats are inhibited by melatonin in vivo and in vitro.
abstract: BACKGROUND
  Our earlier studies indicate that melatonin inhibits the proliferation of prolactinoma and induces apoptosis of pituitary prolactin-secreting tumor in rats. Melatonin has also been shown to induce apoptosis and to reduce the production of ATP in breast tumor cells. This study analyzed the levels of the four mitochondrial respiratory complexes and the production of ATP and also the effects of melatonin treatment of prolactinoma.
  
  
  METHODS
  In the in vivo study, mitochondria were harvested from control pituitaries or prolactinoma collected from the pituitaries of melatonin- and 17-β-estradiol (E2)-treated male rats. In the in vitro study, prolactinoma cells mitochondria were harvested. Activities of the four mitochondrial respiratory complexes were assayed using fluorometer. ATP production of prolactinoma cells was estimated using bioluminescent methods.
  
  
  RESULTS
  Elevated levels of four mitochondrial respiratory complexes activities and ATP production were recorded in prolactinoma cells. Moreover, in both in vivo and in vitro studies, melatonin inhibited the activities of mitochondrial respiratory complexes and the production of ATP in prolactinoma cells.
  
  
  CONCLUSIONS
  There is a link between mitochondrial function increase and tumorigenesis. Melatonin induces apoptosis of pituitary prolactin-secreting tumor of rats via the induction of mitochondrial dysfunction and inhibition of energy metabolism.
authors.affiliation: Department of General Surgery, Shijingshan Teaching Hospital of Capital Medical University, Beijing Shijingshan Hospital, Beijing 100043, China.
authors.forename: Bao-Qiang
authors.initials: BQ
authors.lastname: Wang
authors.affiliation: Department of Critical Care Medicine, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
authors.forename: Quan-Hui
authors.initials: QH
authors.lastname: Yang
authors.affiliation: Department of Physiology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
authors.forename: Rong-Kun
authors.initials: RK
authors.lastname: Xu
authors.affiliation: Department of Toxicology, National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050, China. Email: jnx999@263.net.
authors.forename: Jian-Ning
authors.initials: JN
authors.lastname: Xu
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D004958:Estradiol / Q000627:therapeutic use*; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D015175:Prolactinoma / Q000188:drug therapy* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004958:Estradiol; D000255:Adenosine Triphosphate; D011388:Prolactin; D008550:Melatonin