Cargando…
Icaritin induces lytic cytotoxicity in extranodal NK/T-cell lymphoma
BACKGROUND: Extranodal NK/T-cell lymphoma (ENKL) is an aggressive hematological malignancy associated with Epstein–Barr virus (EBV) infection. It is often resistant to conventional chemotherapy and has a poor prognosis. Icaritin, a compound derived from Chinese herbal medicine, Herba Epimedii, has b...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336495/ https://www.ncbi.nlm.nih.gov/pubmed/25887673 http://dx.doi.org/10.1186/s13046-015-0133-x |
_version_ | 1782358478628585472 |
---|---|
author | Wu, Ting Wang, Songmei Wu, Jinfeng Lin, Zhiguang Sui, Xianxian Xu, Xiaoping Shimizu, Norio Chen, Bobin Wang, Xuanyi |
author_facet | Wu, Ting Wang, Songmei Wu, Jinfeng Lin, Zhiguang Sui, Xianxian Xu, Xiaoping Shimizu, Norio Chen, Bobin Wang, Xuanyi |
author_sort | Wu, Ting |
collection | PubMed |
description | BACKGROUND: Extranodal NK/T-cell lymphoma (ENKL) is an aggressive hematological malignancy associated with Epstein–Barr virus (EBV) infection. It is often resistant to conventional chemotherapy and has a poor prognosis. Icaritin, a compound derived from Chinese herbal medicine, Herba Epimedii, has been reported to exert antitumor effects on a variety of cancer cell lines. In the present study, we investigated the cytotoxic effects of Icaritin on the two EBV-positive ENKL cell lines SNK-10 and SNT-8, along with the underlying molecular mechanisms. METHODS: ENKL cell lines SNK-10 and SNT-8 were exposed to different concentrations of Icaritin for the indicated time. Treated cells were analyzed for cell proliferation, cell cycle, and cell apoptosis. Phosphorylation of Stat3 and Akt proteins in signaling pathways and the EBV-encoded LMP1 proteins were measured by Western blot. Expression of EBV genes was assessed by Real-Time PCR. RESULTS: Our results showed that Icaritin dose-dependently inhibits ENKL cell proliferation and induces apoptosis and cell cycle arrest at G(2)/M phase. Additionally, Icaritin upregulates Bax, downregulates Bcl-2 and pBad, and activates caspase-3 and caspase-9. The anti-proliferative and pro-apoptotic effects of Icaritin are likely mediated by inhibition of Stat3 and Akt pathways through LMP1 downregulation. Importantly, Icaritin induces EBV lytic gene expression in ENKL cells, and the combination of Icaritin and the antiviral drug ganciclovir (GCV) is more effective in inducing ENKL cells apoptosis than Icaritin or GCV alone. CONCLUSIONS: These findings indicate that EBV-targeted approaches may have significant therapeutic potential for ENKL treatment. |
format | Online Article Text |
id | pubmed-4336495 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-43364952015-02-22 Icaritin induces lytic cytotoxicity in extranodal NK/T-cell lymphoma Wu, Ting Wang, Songmei Wu, Jinfeng Lin, Zhiguang Sui, Xianxian Xu, Xiaoping Shimizu, Norio Chen, Bobin Wang, Xuanyi J Exp Clin Cancer Res Research Article BACKGROUND: Extranodal NK/T-cell lymphoma (ENKL) is an aggressive hematological malignancy associated with Epstein–Barr virus (EBV) infection. It is often resistant to conventional chemotherapy and has a poor prognosis. Icaritin, a compound derived from Chinese herbal medicine, Herba Epimedii, has been reported to exert antitumor effects on a variety of cancer cell lines. In the present study, we investigated the cytotoxic effects of Icaritin on the two EBV-positive ENKL cell lines SNK-10 and SNT-8, along with the underlying molecular mechanisms. METHODS: ENKL cell lines SNK-10 and SNT-8 were exposed to different concentrations of Icaritin for the indicated time. Treated cells were analyzed for cell proliferation, cell cycle, and cell apoptosis. Phosphorylation of Stat3 and Akt proteins in signaling pathways and the EBV-encoded LMP1 proteins were measured by Western blot. Expression of EBV genes was assessed by Real-Time PCR. RESULTS: Our results showed that Icaritin dose-dependently inhibits ENKL cell proliferation and induces apoptosis and cell cycle arrest at G(2)/M phase. Additionally, Icaritin upregulates Bax, downregulates Bcl-2 and pBad, and activates caspase-3 and caspase-9. The anti-proliferative and pro-apoptotic effects of Icaritin are likely mediated by inhibition of Stat3 and Akt pathways through LMP1 downregulation. Importantly, Icaritin induces EBV lytic gene expression in ENKL cells, and the combination of Icaritin and the antiviral drug ganciclovir (GCV) is more effective in inducing ENKL cells apoptosis than Icaritin or GCV alone. CONCLUSIONS: These findings indicate that EBV-targeted approaches may have significant therapeutic potential for ENKL treatment. BioMed Central 2015-02-15 /pmc/articles/PMC4336495/ /pubmed/25887673 http://dx.doi.org/10.1186/s13046-015-0133-x Text en © Wu et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Wu, Ting Wang, Songmei Wu, Jinfeng Lin, Zhiguang Sui, Xianxian Xu, Xiaoping Shimizu, Norio Chen, Bobin Wang, Xuanyi Icaritin induces lytic cytotoxicity in extranodal NK/T-cell lymphoma |
title | Icaritin induces lytic cytotoxicity in extranodal NK/T-cell lymphoma |
title_full | Icaritin induces lytic cytotoxicity in extranodal NK/T-cell lymphoma |
title_fullStr | Icaritin induces lytic cytotoxicity in extranodal NK/T-cell lymphoma |
title_full_unstemmed | Icaritin induces lytic cytotoxicity in extranodal NK/T-cell lymphoma |
title_short | Icaritin induces lytic cytotoxicity in extranodal NK/T-cell lymphoma |
title_sort | icaritin induces lytic cytotoxicity in extranodal nk/t-cell lymphoma |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4336495/ https://www.ncbi.nlm.nih.gov/pubmed/25887673 http://dx.doi.org/10.1186/s13046-015-0133-x |
work_keys_str_mv | AT wuting icaritininduceslyticcytotoxicityinextranodalnktcelllymphoma AT wangsongmei icaritininduceslyticcytotoxicityinextranodalnktcelllymphoma AT wujinfeng icaritininduceslyticcytotoxicityinextranodalnktcelllymphoma AT linzhiguang icaritininduceslyticcytotoxicityinextranodalnktcelllymphoma AT suixianxian icaritininduceslyticcytotoxicityinextranodalnktcelllymphoma AT xuxiaoping icaritininduceslyticcytotoxicityinextranodalnktcelllymphoma AT shimizunorio icaritininduceslyticcytotoxicityinextranodalnktcelllymphoma AT chenbobin icaritininduceslyticcytotoxicityinextranodalnktcelllymphoma AT wangxuanyi icaritininduceslyticcytotoxicityinextranodalnktcelllymphoma |