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
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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