title: Antitumoral action of icaritin in LNCaP prostate cancer cells by regulating PEA3/HER2/AR signaling.
abstract: Human epidermal growth factor receptor type 2 (HER2) and androgen receptor (AR) are critical factors for prostate cancer (PCa) progression. These factors regulate tumor cell survival and proliferation, and remain as crucial drivers of castration-resistant PCa progression. Icaritin (ICT) is a prenyl flavonoid derived from the Epimedium genus, which has many biological and pharmacological effects. Using androgen-sensitive human prostate carcinoma LNCaP cell lines, we found that 35 μg/ml of ICT could inhibit more than 50% of cell proliferation, induce cell apoptosis, and lead to a strong G1 phase arrest by targeting cyclin-related proteins and suppressing the ability of cell invasion. Moreover, ICT exerts its potent anticancer efficacy by inducing polyomavirus enhancer activator 3 (PEA3) to inhibit the aberrantly activated HER2/AR signaling. In addition, after PEA3 expression was silenced by specific small-interference RNA, we found that both the ICT-inhibited effect on LNCaP cell proliferation and the ICT-induced cell apoptosis rate decreased. These results provide alternative mechanisms for the antitumor actions of ICT, indicating that ICT might be a promising therapeutic agent, as well as a preventive agent, for hormone therapy-resistant PCa.
authors.affiliation: Department of Urology, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.
authors.forename: Jimeng
authors.initials: J
authors.lastname: Hu
authors.forename: Wenhui
authors.initials: W
authors.lastname: Zhu
authors.forename: Bingbing
authors.initials: B
authors.lastname: Wei
authors.forename: Hui
authors.initials: H
authors.lastname: Wen
authors.forename: Shanhua
authors.initials: S
authors.lastname: Mao
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
authors.forename: Mengbo
authors.initials: M
authors.lastname: Hu
authors.forename: Tian
authors.initials: T
authors.lastname: Yang
authors.forename: Haowen
authors.initials: H
authors.lastname: Jiang
mesh_terms: D017500:Adenovirus E1A Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D064129:Prostatic Neoplasms, Castration-Resistant / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D017500:Adenovirus E1A Proteins; D005419:Flavonoids; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D018719:Erb-b2 Receptor Tyrosine Kinases; D011944:Receptors, Androgen; C410798:AR protein, human; C079853:ETV4 protein, human; C508053:ERBB2 protein, human; C499403:icaritin