A precisely substituted benzopyran targets androgen refractory prostate cancer cells through selective modulation of estrogen receptors
Autor: | Vikas Sharma, Vikas Verma, Vishnu L. Sharma, Vishal Singh, Jagdamba P. Maikhuri, Gopal Gupta, Amit Sarswat, Rajeev Kumar, Ashish Jain |
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Rok vydání: | 2014 |
Předmět: |
Male
Selective Estrogen Receptor Modulators medicine.medical_specialty Time Factors Antineoplastic Agents Hormonal Estrogen receptor Genistein Apoptosis Biology Toxicology Transfection chemistry.chemical_compound Prostate cancer Structure-Activity Relationship Internal medicine Cell Line Tumor Chlorocebus aethiops medicine Animals Estrogen Receptor beta Humans Benzopyrans Receptor Estrogen receptor beta Cell Proliferation Pharmacology Dose-Response Relationship Drug Molecular Structure Estrogen Receptor alpha Cell Cycle Checkpoints medicine.disease Prostatic Neoplasms Castration-Resistant Endocrinology chemistry Drug Design COS Cells Cancer research Phytoestrogens RNA Interference Estrogen receptor alpha hormones hormone substitutes and hormone antagonists Tamoxifen medicine.drug Signal Transduction |
Zdroj: | Toxicology and applied pharmacology. 283(3) |
ISSN: | 1096-0333 |
Popis: | Dietary consumption of phytoestrogens like genistein has been linked with lower incidence of prostate cancer. The estradiol-like benzopyran core of genistein confers estrogen receptor-β (ER-β) selectivity that imparts weak anti-proliferative activity against prostate cancer cells. DL-2-[4-(2-piperidinoethoxy)phenyl]-3-phenyl-2H-1-benzopyran (BP), a SERM designed with benzopyran core, targeted androgen independent prostate cancer (PC-3) cells 14-times more potently than genistein, ~25% more efficiently than tamoxifen and 6.5-times more actively than ICI-182780, without forfeiting significant specificity in comparison to genistein. BP increased apoptosis (annexin-V and TUNEL labeling), arrested cell cycle, and significantly increased caspase-3 activity along with mRNA expressions of estrogen receptor (ER)-β and FasL (qPCR) in PC-3 cells. In classical ERE-luc reporter assay BP behaved as a potent ER-α antagonist and ER-β agonist. Accordingly, it decreased expression of ER-α target PS2 (P |
Databáze: | OpenAIRE |
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