Abstract
BackgroundThe aim of this study is to determine anti-cancer effect of Icariside II purified from the root of Epimedium koreanum Nakai on human acute myeloid leukemia (AML) cell line U937.Methodology/Principal FindingsIcariside II blocked the growth U937 cells in a dose- and time-dependent manner. In this anti-proliferation process, this herb compound rendered the cells susceptible to apoptosis, manifested by enhanced accumulation of sub-G1 cell population and increased the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells. Icariside II was able to activate caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) in a time-dependent manner. Concurrently, the anti-apoptotic proteins, such as bcl-xL and survivin in U937 cells, were downregulated by Icariside II. In addition, Icariside II could inhibit STAT3 phosphorylation and function and subsequently suppress the activation of Janus activated kinase 2 (JAK2), the upstream activators of STAT3, in a dose- and time-dependent manner. Icariside II also enhanced the expression of protein tyrosine phosphatase (PTP) SH2 domain-containing phosphatase (SHP)-1, and the addition of sodium pervanadate (a PTP inhibitor) prevented Icariside II-induced apoptosis as well as STAT3 inactivation in STAT3 positive U937 cells. Furthermore, silencing SHP-1 using its specific siRNA significantly blocked STAT3 inactivation and apoptosis induced by Icariside II in U937 cells.Conclusions/SignificanceOur results demonstrated that via targeting STAT3-related signaling, Icariside II sensitizes U937 cells to apoptosis and perhaps serves as a potent chemotherapeutic agent for AML.
Highlights
Icariside II, a flavonoid compound, is derived from the stems and leaves of Epimedium koreanum that has been traditionally utilized for neurasthenia, amnesia and impotence in Oriental medicine [1,2]
transferase dUTP nick end labeling (TUNEL) assay further confirmed the occurrence of apoptosis after U937 cells were treated with Icariside that increased the number of fluorescein isothiocyanate (FITC)-stained, TUNEL positive cells in a timedependent manner (Fig. 2B)
The underlying mechanisms of Icariside IIinduced anti-cancer activity were investigated in U937 acute myeloid leukemia (AML) cells
Summary
Icariside II, a flavonoid compound, is derived from the stems and leaves of Epimedium koreanum that has been traditionally utilized for neurasthenia, amnesia and impotence in Oriental medicine [1,2]. We and others recently reported that Icariside II appeared to possess anti-cancer activity against multiple myeloma [5], prostate cancer [6] and osteosarcoma cells [7]. Many groups have suggested the potential of natural products as potent chemotherapeutic drugs for AML to improve the therapeutic efficacy and lower the side effects. Wogonin, an active compound in Scutellaria baicalensis, induced apoptosis by inhibiting telomerase activity in HL-60 AML cells [9] and ajoene, a natural garlic compound, was suggested as an anti-leukemic agent for AML therapy [10]. The aim of this study is to determine anti-cancer effect of Icariside II purified from the root of Epimedium koreanum Nakai on human acute myeloid leukemia (AML) cell line U937
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.
