title: Apoptosis induction and inhibition of hyperplasia formation by 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H-benzo(b)pyran in rat uterus.
abstract: OBJECTIVE
  The study was undertaken to explore the antiproliferative mechanism of action of 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H-benzo(b)pyran (K-1) in estradiol-induced rat uterine hyperplasia.
  
  
  METHODS
  Adult ovariectomized rats received vehicle or estradiol alone (20 μg/kg) or estradiol along with K-1 (100 or 200 μg/kg) for 14 days. Uterine histomorphometric analysis and immunoblotting were performed. Caspase-3 activity and terminal deoxynucleotidyl transferase-mediated nick end-labeling staining were performed to analyze the apoptotic potential of compound.
  
  
  RESULTS
  Compound inhibited estradiol-induced uterine weight and histomorphometric changes pertaining to endometrial growth and down-regulated the expression of estrogen response element and activator protein-1 regulated genes and transcription factors. The compound significantly induced apoptosis, interfered with Akt activation, decreased X-linked inhibitor of apoptosis protein expression leading to an increased cleavage of caspase-9, caspase-3, poly(adenosine diphosphate-ribose) polymerase, increased Bax/Bcl2 ratio, and caspase-3 activity.
  
  
  CONCLUSIONS
  K-1 inhibits endometrial proliferation via nonclassical estrogen receptor signaling mechanisms. It interfered with Akt activation and induced apoptosis via the intrinsic pathway and inhibited estradiol-induced hyperplasia formation in rat uterus.
authors.affiliation: Division of Endocrinology, Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow, India.
authors.forename: Vishal
authors.initials: V
authors.lastname: Chandra
authors.forename: Iram
authors.initials: I
authors.lastname: Fatima
authors.forename: Ruchi
authors.initials: R
authors.lastname: Saxena
authors.forename: Shakti
authors.initials: S
authors.lastname: Kitchlu
authors.forename: Sharad
authors.initials: S
authors.lastname: Sharma
authors.forename: Mohammad Kamil
authors.initials: MK
authors.lastname: Hussain
authors.forename: Kanchan
authors.initials: K
authors.lastname: Hajela
authors.forename: Preeti
authors.initials: P
authors.lastname: Bajpai
authors.forename: Anila
authors.initials: A
authors.lastname: Dwivedi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001578:Benzopyrans / Q000494:pharmacology*; D005260:Female; D006965:Hyperplasia / Q000517:prevention & control*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014599:Uterus / Q000187:drug effects* / Q000473:pathology*
chemical_list: D001578:Benzopyrans; D010880:Piperidines; C066625:2-(4-(2-piperidinoethoxy)phenyl)-3-(4-hydroxyphenyl)-2H-1-benzopyran