Apoptosis induction and inhibition of hyperplasia formation by 2-[piperidinoethoxyphenyl]-3-[4-hydroxyphenyl]-2H-benzo(b)pyran in rat uterus

作者：Chandra Vishal; Fatima Iram; Saxena Ruchi; Kitchlu Shakti; Sharma Sharad; Hussain Mohammad Kamil; Hajela Kanchan; Bajpai Preeti; Dwivedi Anila^*

来源：American Journal of Obstetrics and Gynecology, 2011, 205(4): 362.e1.

DOI：10.1016/j.ajog.2011.05.024

• apoptosis
• endometrial hyperplasia
• rat

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. STUDY
DESIGN: Adult ovariectomized rats received vehicle or estradiol alone (20 mu g/kg) or estradiol along with K-1 (100 or 200 mu g/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 acti-vator 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.
CONCLUSION: 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.

• 出版日期2011-10