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A novel anti-cancer agent Icaritin suppresses hepatocellular carcinoma initiation and malignant growth through the IL-6/Jak2/Stat3 pathway

Tumor-initiating cell (TIC) is a subpopulation of cells in tumors that are responsible for tumor initiation and progression. Recent studies indicate that hepatocellular carcinoma-initiating cells (HCICs) confer the high malignancy, recurrence and multi-drug resistance in hepatocellular carcinoma (HC...

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Autores principales: Zhao, Hong, Guo, Yuming, Li, Shu, Han, Ruiqin, Ying, Jianming, Zhu, Hai, Wang, Yuanyuan, Yin, Li, Han, Yuqing, Sun, Lingzhi, Wang, Zhaoyi, Lin, Qingcong, Bi, Xinyu, Jiao, Yuchen, Jia, Hongying, Zhao, Jianjun, Huang, Zhen, Li, Zhiyu, Zhou, Jianguo, Song, Wei, Meng, Kun, Cai, Jianqiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741651/
https://www.ncbi.nlm.nih.gov/pubmed/26376676
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author Zhao, Hong
Guo, Yuming
Li, Shu
Han, Ruiqin
Ying, Jianming
Zhu, Hai
Wang, Yuanyuan
Yin, Li
Han, Yuqing
Sun, Lingzhi
Wang, Zhaoyi
Lin, Qingcong
Bi, Xinyu
Jiao, Yuchen
Jia, Hongying
Zhao, Jianjun
Huang, Zhen
Li, Zhiyu
Zhou, Jianguo
Song, Wei
Meng, Kun
Cai, Jianqiang
author_facet Zhao, Hong
Guo, Yuming
Li, Shu
Han, Ruiqin
Ying, Jianming
Zhu, Hai
Wang, Yuanyuan
Yin, Li
Han, Yuqing
Sun, Lingzhi
Wang, Zhaoyi
Lin, Qingcong
Bi, Xinyu
Jiao, Yuchen
Jia, Hongying
Zhao, Jianjun
Huang, Zhen
Li, Zhiyu
Zhou, Jianguo
Song, Wei
Meng, Kun
Cai, Jianqiang
author_sort Zhao, Hong
collection PubMed
description Tumor-initiating cell (TIC) is a subpopulation of cells in tumors that are responsible for tumor initiation and progression. Recent studies indicate that hepatocellular carcinoma-initiating cells (HCICs) confer the high malignancy, recurrence and multi-drug resistance in hepatocellular carcinoma (HCC). In this study, we found that Icaritin, a prenylflavonoid derivative from Epimedium Genus, inhibited malignant growth of HCICs. Icaritin decreased the proportion of EpCAM-positive (a HCICs marker) cells, suppressed tumorsphere formation in vitro and tumor formation in vivo. We also found that Icaritin reduced expression of Interleukin-6 Receptors (IL-6Rs), attenuated both constitutive and IL-6-induced phosphorylation of Janus-activated kinases 2 (Jak2) and Signal transducer and activator of transcription 3 (Stat3), and inhibited Stat3 downstream genes, such as Bmi-1 and Oct4. The inhibitory activity of Icaritin in HCICs was augmented by siRNA-mediated silencing of Stat3 but attenuated by constitutive activation of Stat3. Taken together, our results indicate that Icaritin is able to inhibit malignant growth of HCICs and suggest that Icaritin may be developed into a novel therapeutic agent for effective treatment of HCC.
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spelling pubmed-47416512016-03-03 A novel anti-cancer agent Icaritin suppresses hepatocellular carcinoma initiation and malignant growth through the IL-6/Jak2/Stat3 pathway Zhao, Hong Guo, Yuming Li, Shu Han, Ruiqin Ying, Jianming Zhu, Hai Wang, Yuanyuan Yin, Li Han, Yuqing Sun, Lingzhi Wang, Zhaoyi Lin, Qingcong Bi, Xinyu Jiao, Yuchen Jia, Hongying Zhao, Jianjun Huang, Zhen Li, Zhiyu Zhou, Jianguo Song, Wei Meng, Kun Cai, Jianqiang Oncotarget Research Paper Tumor-initiating cell (TIC) is a subpopulation of cells in tumors that are responsible for tumor initiation and progression. Recent studies indicate that hepatocellular carcinoma-initiating cells (HCICs) confer the high malignancy, recurrence and multi-drug resistance in hepatocellular carcinoma (HCC). In this study, we found that Icaritin, a prenylflavonoid derivative from Epimedium Genus, inhibited malignant growth of HCICs. Icaritin decreased the proportion of EpCAM-positive (a HCICs marker) cells, suppressed tumorsphere formation in vitro and tumor formation in vivo. We also found that Icaritin reduced expression of Interleukin-6 Receptors (IL-6Rs), attenuated both constitutive and IL-6-induced phosphorylation of Janus-activated kinases 2 (Jak2) and Signal transducer and activator of transcription 3 (Stat3), and inhibited Stat3 downstream genes, such as Bmi-1 and Oct4. The inhibitory activity of Icaritin in HCICs was augmented by siRNA-mediated silencing of Stat3 but attenuated by constitutive activation of Stat3. Taken together, our results indicate that Icaritin is able to inhibit malignant growth of HCICs and suggest that Icaritin may be developed into a novel therapeutic agent for effective treatment of HCC. Impact Journals LLC 2015-09-10 /pmc/articles/PMC4741651/ /pubmed/26376676 Text en Copyright: © 2015 Zhao et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Zhao, Hong
Guo, Yuming
Li, Shu
Han, Ruiqin
Ying, Jianming
Zhu, Hai
Wang, Yuanyuan
Yin, Li
Han, Yuqing
Sun, Lingzhi
Wang, Zhaoyi
Lin, Qingcong
Bi, Xinyu
Jiao, Yuchen
Jia, Hongying
Zhao, Jianjun
Huang, Zhen
Li, Zhiyu
Zhou, Jianguo
Song, Wei
Meng, Kun
Cai, Jianqiang
A novel anti-cancer agent Icaritin suppresses hepatocellular carcinoma initiation and malignant growth through the IL-6/Jak2/Stat3 pathway
title A novel anti-cancer agent Icaritin suppresses hepatocellular carcinoma initiation and malignant growth through the IL-6/Jak2/Stat3 pathway
title_full A novel anti-cancer agent Icaritin suppresses hepatocellular carcinoma initiation and malignant growth through the IL-6/Jak2/Stat3 pathway
title_fullStr A novel anti-cancer agent Icaritin suppresses hepatocellular carcinoma initiation and malignant growth through the IL-6/Jak2/Stat3 pathway
title_full_unstemmed A novel anti-cancer agent Icaritin suppresses hepatocellular carcinoma initiation and malignant growth through the IL-6/Jak2/Stat3 pathway
title_short A novel anti-cancer agent Icaritin suppresses hepatocellular carcinoma initiation and malignant growth through the IL-6/Jak2/Stat3 pathway
title_sort novel anti-cancer agent icaritin suppresses hepatocellular carcinoma initiation and malignant growth through the il-6/jak2/stat3 pathway
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741651/
https://www.ncbi.nlm.nih.gov/pubmed/26376676
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