Icaritin suppresses multiple myeloma, by inhibiting IL-6/JAK2/STAT3

作者: Shicong Zhu , Zhihua Wang , Zijian Li , Hongling Peng , Yunya Luo

DOI: 10.18632/ONCOTARGET.3399

关键词:

摘要: Icaritin is an active prenylflavonoid derived from Epimedium genus, a traditional Chinese medicine. has wide range of pharmacological and biological activities, including cardiovascular function improvement, hormone regulation antitumor activity. Here, we investigated the effect icaritin on multiple myeloma (MM) in vitro vivo. inhibited cell growth MM line primary cells. In contrast, had low or no cytotoxic normal hematopoiesis. We also demonstrated that xenograft mouse models, suppressed tumor decreased serum IL-6 IgE levels, but did not show adverse reactions such as body weight loss. The anti-MM activity was mainly mediated by inhibiting IL-6/JAK2/STAT3 signaling. suggest can be further tested clinical trials MM.

参考文章(41)
Verena Wagner, Dirk Hose, Anja Seckinger, Ludmila Weiz, Tobias Meißner, Thiery Rème, Iris Breitkreutz, Klaus Podar, Anthony D. Ho, Hartmut Goldschmidt, Alwin Krämer, Bernard Klein, Marc S. Raab, Preclinical efficacy of sepantronium bromide (YM155) in multiple myeloma is conferred by down regulation of Mcl-1 Oncotarget. ,vol. 5, pp. 10237- 10250 ,(2014) , 10.18632/ONCOTARGET.2529
Nika N Danial, Stanley J Korsmeyer, Cell Death: Critical Control Points Cell. ,vol. 116, pp. 205- 219 ,(2004) , 10.1016/S0092-8674(04)00046-7
Lei Shi, Siqing Wang, Maurizio Zangari, Hongwei Xu, Thai M. Cao, Chunjiao Xu, Yong Wu, Fang Xiao, Yinghong Liu, Ye Yang, Mohamed Salama, Guiyuan Li, Guido Tricot, Fenghuang Zhan, Over-expression of CKS1B activates both MEK/ERK and JAK/STAT3 signaling pathways and promotes myeloma cell drug-resistance Oncotarget. ,vol. 1, pp. 22- 33 ,(2010) , 10.18632/ONCOTARGET.105
Jian Huang, Lan Yuan, Xi Wang, Tian-Lan Zhang, Kui Wang, Icaritin and its glycosides enhance osteoblastic, but suppress osteoclastic, differentiation and activity in vitro. Life Sciences. ,vol. 81, pp. 832- 840 ,(2007) , 10.1016/J.LFS.2007.07.015
Rhona Stein, Pankaj Gupta, Xiaochuan Chen, Thomas M. Cardillo, Richard R. Furman, Susan Chen, Chien-Hsing Chang, David M. Goldenberg, Therapy of B-Cell Malignancies by Anti-HLA-DR Humanized Monoclonal Antibody, IMMU-114, Is Mediated through Hyperactivation of ERK and JNK MAP Kinase Signaling Pathways. Blood. ,vol. 115, pp. 5180- 5190 ,(2009) , 10.1182/BLOOD-2009-06-228288
Jacqueline Bromberg, Timothy C. Wang, Inflammation and cancer: IL-6 and STAT3 complete the link. Cancer Cell. ,vol. 15, pp. 79- 80 ,(2009) , 10.1016/J.CCR.2009.01.009
Jian feng Zhu, Zi jian Li, Guang sen Zhang, Kun Meng, Wen yong Kuang, Jin Li, Xin fu Zhou, Rui juan Li, Hong ling Peng, Chong wen Dai, Jian Kai Shen, Fan jie Gong, Yun xiao Xu, Su fang Liu, Icaritin shows potent anti-leukemia activity on chronic myeloid leukemia in vitro and in vivo by regulating MAPK/ERK/JNK and JAK2/STAT3 /AKT signalings. PLOS ONE. ,vol. 6, ,(2011) , 10.1371/JOURNAL.PONE.0023720
Alok C. Bharti, Shishir Shishodia, James M. Reuben, Donna Weber, Raymond Alexanian, Saroj Raj-Vadhan, Zeev Estrov, Moshe Talpaz, Bharat B. Aggarwal, Nuclear factor–κB and STAT3 are constitutively active in CD138+cells derived from multiple myeloma patients, and suppression of these transcription factors leads to apoptosis Blood. ,vol. 103, pp. 3175- 3184 ,(2004) , 10.1182/BLOOD-2003-06-2151
Qihui Li, Lei Huai, Cuiping Zhang, Cuicui Wang, Yujjao Jia, Yirui Chen, Pei Yu, Houcai Wang, Qing Rao, Min Wang, Jianxiang Wang, None, Icaritin induces AML cell apoptosis via the MAPK/ERK and PI3K/AKT signal pathways International Journal of Hematology. ,vol. 97, pp. 617- 623 ,(2013) , 10.1007/S12185-013-1317-9