Identification of 11(13)-dehydroivaxillin as a potent therapeutic agent against non-Hodgkin's lymphoma
| Autor: | Hui-Zi Jin, Wei-Dong Zhang, Xinhua Xiao, Wei Liu, Ying-Li Wu, Chunmin Ma, Miao Yu, Hanzhang Xu, Jin Jin, Yin Tong, Hui-Liang Li, Li Zhou, Hu Lei |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Cancer Research Transcription Genetic Cell Survival Immunology Cell Apoptosis Mice SCID Biology 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound immune system diseases hemic and lymphatic diseases Cell Line Tumor medicine Animals Humans Protein kinase B PI3K/AKT/mTOR pathway Cell Proliferation Cell growth Tumor Necrosis Factor-alpha RELB Lymphoma Non-Hodgkin NF-kappa B Cell Biology medicine.disease Xenograft Model Antitumor Assays humanities Non-Hodgkin's lymphoma Cell biology I-kappa B Kinase Enzyme Activation 030104 developmental biology medicine.anatomical_structure chemistry Gene Knockdown Techniques Cancer research Original Article Growth inhibition Sesquiterpenes |
| Zdroj: | Cell Death & Disease |
| ISSN: | 2041-4889 |
| Popis: | Despite great advancements in the treatment of non-Hodgkin lymphoma (NHL), sensitivity of different subtypes to therapy varies. Targeting the aberrant activation NF-κB signaling pathways in lymphoid malignancies is a promising strategy. Here, we report that 11(13)-dehydroivaxillin (DHI), a natural compound isolated from the Carpesium genus, induces growth inhibition and apoptosis of NHL cells. Multiple signaling cascades are influenced by DHI in NHL cells. PI3K/AKT and ERK are activated or inhibited in a cell type dependent manner, whereas NF-κB signaling pathway was inhibited in all the NHL cells tested. Applying the cellular thermal shift assay, we further demonstrated that DHI directly interacts with IKKα/IKKβ in NHL cells. Interestingly, DHI treatment also reduced the IKKα/IKKβ protein level in NHL cells. Consistent with this finding, knockdown of IKKα/IKKβ inhibits cell proliferation and enhances DHI-induced proliferation inhibition. Overexpression of p65, p52 or RelB partially reverses DHI-induced cell growth inhibition. Furthermore, DHI treatment significantly inhibits the growth of NHL cell xenografts. In conclusion, we demonstrate that DHI exerts anti-NHL effect in vitro and in vivo, through a cumulative effect on NF-κB and other pathways. DHI may serve as a promising lead compound for the therapy of NHL. |
| Databáze: | OpenAIRE |
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