Icariside II induces apoptosis in U937 acute myeloid leukemia cells: role of inactivation of STAT3-related signaling.
BACKGROUND: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. METHODOLOGY/PRINCIPAL FINDINGS:Icariside II blocked the growth U937 cells in a dose- and time-dependent manner....
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3320887?pdf=render |
| _version_ | 1818556274590089216 |
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| author | Sang-Hun Kang Soo-Jin Jeong Sun-Hee Kim Ji-Hyun Kim Ji Hoon Jung Wonil Koh Jung Hyo Kim Dae Keun Kim Chang-Yan Chen Sung-Hoon Kim |
| author_facet | Sang-Hun Kang Soo-Jin Jeong Sun-Hee Kim Ji-Hyun Kim Ji Hoon Jung Wonil Koh Jung Hyo Kim Dae Keun Kim Chang-Yan Chen Sung-Hoon Kim |
| author_sort | Sang-Hun Kang |
| collection | DOAJ |
| description | BACKGROUND: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. METHODOLOGY/PRINCIPAL FINDINGS:Icariside 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-x(L) 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/SIGNIFICANCE:Our 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. |
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| format | Article |
| id | doaj.art-3c9844108b5a4c6da83911dfc36ae7a9 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T23:45:14Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-3c9844108b5a4c6da83911dfc36ae7a92022-12-21T23:27:01ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0174e2870610.1371/journal.pone.0028706Icariside II induces apoptosis in U937 acute myeloid leukemia cells: role of inactivation of STAT3-related signaling.Sang-Hun KangSoo-Jin JeongSun-Hee KimJi-Hyun KimJi Hoon JungWonil KohJung Hyo KimDae Keun KimChang-Yan ChenSung-Hoon KimBACKGROUND: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. METHODOLOGY/PRINCIPAL FINDINGS:Icariside 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-x(L) 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/SIGNIFICANCE:Our 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.http://europepmc.org/articles/PMC3320887?pdf=render |
| spellingShingle | Sang-Hun Kang Soo-Jin Jeong Sun-Hee Kim Ji-Hyun Kim Ji Hoon Jung Wonil Koh Jung Hyo Kim Dae Keun Kim Chang-Yan Chen Sung-Hoon Kim Icariside II induces apoptosis in U937 acute myeloid leukemia cells: role of inactivation of STAT3-related signaling. PLoS ONE |
| title | Icariside II induces apoptosis in U937 acute myeloid leukemia cells: role of inactivation of STAT3-related signaling. |
| title_full | Icariside II induces apoptosis in U937 acute myeloid leukemia cells: role of inactivation of STAT3-related signaling. |
| title_fullStr | Icariside II induces apoptosis in U937 acute myeloid leukemia cells: role of inactivation of STAT3-related signaling. |
| title_full_unstemmed | Icariside II induces apoptosis in U937 acute myeloid leukemia cells: role of inactivation of STAT3-related signaling. |
| title_short | Icariside II induces apoptosis in U937 acute myeloid leukemia cells: role of inactivation of STAT3-related signaling. |
| title_sort | icariside ii induces apoptosis in u937 acute myeloid leukemia cells role of inactivation of stat3 related signaling |
| url | http://europepmc.org/articles/PMC3320887?pdf=render |
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