Abstract
Icaritin, a compound from Epimedium Genus, has selective estrogen receptor (ER) modulating activities, and posses anti-tumor activity. Here, we examined icaritin effect on cell growth of human endometrial cancer Hec1A cells and found that icaritin potently inhibited proliferation of Hec1A cells. Icaritin-inhibited cell growth was associated with increased levels of p21 and p27 expression and reduced cyclinD1 and cdk 4 expression. Icaritin also induced cell apoptosis accompanied by activation of caspases as evidenced by the cleavage of endogenous substrate Poly (ADP-ribose) polymerase (PARP) and cytochrome c release, which was abrogated by pretreatment with the pan-caspase inhibitor z-VAD-fmk. Icaritin treatment also induced expression of pro-apoptotic protein Bax with a concomitant decrease of Bcl-2 expression. Furthermore, icaritin induced sustained phosphorylation of extracellular signal-regulated kinase1/2 (the MAPK/ ERK1/2) in Hec1A cells and U0126, a specific MAP kinase kinase (MEK1/2) inhibitor, blocked the ERK1/2 activation by icaritin and abolished the icaritin-induced growth inhibition and apoptosis. Our results demonstrated that icaritin induced sustained ERK 1/2 activation and inhibited growth of endometrial cancer Hec1A cells, and provided a rational for preclinical and clinical evaluation of icaritin for endometrial cancer therapy.
Highlights
Endometrial cancer is one of the most common female pelvic malignancies and is the fourth most common type of cancer in North American women behind lung, breast, and colon cancers, with 42,160 new cases and 7,780 deaths estimated for 2009 [1,2,3]
We demonstrated that icaritin, a compound purified from medicinal herb Epimedium, induces growth inhibition and apoptotic cell death in human endometrial cancer Hec1A cells at a dose and time dependent manner
The observed inhibitory effects of icaritin on the expression of cyclin D1 and cdk4 in Hec1A cells suggested that icaritin may arrest the cell cycle at a specific phase
Summary
Endometrial cancer is one of the most common female pelvic malignancies and is the fourth most common type of cancer in North American women behind lung, breast, and colon cancers, with 42,160 new cases and 7,780 deaths estimated for 2009 [1,2,3]. Patients diagnosed with and treated for early stagedisease of the endometrioid histology enjoy relatively good survival rates, patients with advanced (stage III or IV, according to the newly revised system by the International Federation of Gynecology and Obstetrics [FIGO]) or recurrent endometrial cancer have a poor prognosis [5]. For those women with early stage disease, surgery with individualized use of volume directed radiotherapy is curative [6]. It is urgent to develop novel therapeutic agents to effectively treat this deadly disease
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
