Icaritin induces growth inhibition and apoptosis of human prostatic smooth muscle cells in an estrogen receptor-independent manner.
Icaritin has selective estrogen receptor (ER) modulating activity. ERs are expressed in the prostate stroma, and estrogens have an important role in the pathology of benign prostatic hyperplasia (BPH). However, the impact of icaritin on BPH was not studied. Human prostatic smooth muscle cells (PSMCs) were treated with 0-100 microM icaritin, also using 10 microM ICI182780 as a specific ER antagonist. The effects on cell growth and apoptosis were determined by cell counting and sandwich-enzyme-immunoassay. Western blotting was employed to illustrate the possible mechanisms. Cell growth was strongly inhibited by icaritin, and this was accompanied by an augmented apoptosis. Few changes in icaritin-induced growth inhibition and apoptosis were observed after pretreatment in the presence of ICI182780. Consistent with growth inhibition and apoptosis induction, icaritin decreased cyclin D1 and CDK4 expression and increased Bax/Bcl-2 ratio in human PSMCs. Furthermore, icaritin induced sustained phosphorylation of extracellular signal-regulated kinase (ERK) in human PSMCs. PD98059, a specific ERK inhibitor, blocked the activation of ERK by icaritin and abolished the icaritin-induced growth inhibition and apoptosis. The results indicate that icaritin reduces growth and induces apoptosis in human PSMCs via ERK signaling pathway without involvement of ERs.
Chen
Min-Feng
MF
Department of Urology, Xiangya Hospital, Central South University, 87# Xiangya Road, 410008, Changsha, Hunan, People's Republic of China.
Qi
Lin
L
Li
Yuan
Y
Zu
Xiong-Bing
XB
Dai
Yuan-Qin
YQ
Zhang
Peng
P
D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects*; D011467:Prostate / Q000166:cytology / Q000187:drug effects*; D011960:Receptors, Estrogen / Q000502:physiology*; D015398:Signal Transduction
D005419:Flavonoids; D011960:Receptors, Estrogen; D048049:Extracellular Signal-Regulated MAP Kinases; C499403:icaritin