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Novel selective estrogen receptor modulators induce LNCaP cell death via mechanisms involving apoptosis
Author(s) -
Green Jennifer Evette,
Cooperwood John S.,
Stephenson Adrienne P.,
Reams R. Renee
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.799.9
Subject(s) - viability assay , lncap , apoptosis , acridine orange , programmed cell death , selective estrogen receptor modulator , tamoxifen , cancer research , chemistry , pharmacology , raloxifene , antiestrogen , cell growth , estrogen receptor , medicine , prostate cancer , cancer , breast cancer , biochemistry
Selective Estrogen Modulators (SERMs) offer an alternative approach for treating prostate cancer that differs from the treatment options that are currently available. Using the LNCaP cell line we evaluated three novel SERMs, 3‐[2‐diethylamino]‐ethoxy]‐]‐ D 1,3,5(10)‐estrien‐17‐one (DE), 3‐[2‐diisopropylamino]‐ethoxy‐ D 1,3,5(10)‐estrien‐17‐one (DI) and 17‐b‐3‐[2‐piperidinyl]‐ethoxy]‐ ]‐ D 1,3,5(10)‐estrien‐17‐ol (EPOH), which are aminoalkyloxy derivatives of 1,3,5(10)‐Estratrien. The cytotoxic effect (judged by cell viability) of DE, DI, EPOH and 4‐hydroxytamoxifen (4‐OHT) was determined using the Alamar Blue assay. The effect of the SERMs on apoptosis was determined by Acridine Orange and Ethidium Bromide (AO/EB) staining method. It was observed in comparison to the control, that the three experimental compounds caused a dose‐dependent decrease in cell viability (EC 50 values ranging between 300 μM – 400 μM). AO/EB staining indicated the induction of apoptosis at the same concentrations that caused the dose‐dependent increase in cell death by DE, DI and EPOH. Taken together these results indicate that the novel SERMs cause cell death via underlying mechanisms that lead to apoptosis/programmed cell death and with further evaluation will reveal the potential of these novel SERMs for the treatment of prostate cancer. Supported by NIH/NCRR/RCMI Grant (G12 RR0 3020).