Molecular Mechanism of the Cell Death Induced by the Histone Deacetylase Pan Inhibitor LBH589 (Panobinostat) in Wilms Tumor Cells.
Wilms tumor (WT) is an embryonic kidney cancer, for which histone acetylation might be a therapeutic target. LBH589, a novel targeted agent, suppresses histone deacetylases in many tumors. This study investigated the antitumor activity of LBH589 in SK-NEP-1 and G401 cells.SK-NEP-1 and G401 cell grow...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4503685?pdf=render |
| _version_ | 1819213198744616960 |
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| author | Tao Yan-Fang Li Zhi-Heng Xu Li-Xiao Fang Fang Lu Jun Li Gang Cao Lan Wang Na-Na Du Xiao-Juan Sun Li-Chao Zhao Wen-Li Xiao Pei-Fang Zhao He Su Guang-Hao Li Yan-Hong Li Yi-Ping Xu Yun-Yun Zhou Hui-Ting Wu Yi Jin Mei-Fang Liu Lin Ni Jian Hu Shao-Yan Zhu Xue-Ming Feng Xing Wang Jian Pan Jian |
| author_facet | Tao Yan-Fang Li Zhi-Heng Xu Li-Xiao Fang Fang Lu Jun Li Gang Cao Lan Wang Na-Na Du Xiao-Juan Sun Li-Chao Zhao Wen-Li Xiao Pei-Fang Zhao He Su Guang-Hao Li Yan-Hong Li Yi-Ping Xu Yun-Yun Zhou Hui-Ting Wu Yi Jin Mei-Fang Liu Lin Ni Jian Hu Shao-Yan Zhu Xue-Ming Feng Xing Wang Jian Pan Jian |
| author_sort | Tao Yan-Fang |
| collection | DOAJ |
| description | Wilms tumor (WT) is an embryonic kidney cancer, for which histone acetylation might be a therapeutic target. LBH589, a novel targeted agent, suppresses histone deacetylases in many tumors. This study investigated the antitumor activity of LBH589 in SK-NEP-1 and G401 cells.SK-NEP-1 and G401 cell growth was assessed by CCK-8 and in nude mice experiments. Annexin V/propidium iodide staining followed by flow cytometry detected apoptosis in cell culture. Gene expressions of LBH589-treated tumor cells were analyzed using an Arraystar Human LncRNA Array. The Multi Experiment View cluster software analyzed the expression data. Differentially expressed genes from the cluster analyses were imported into the Ingenuity Pathway Analysis tool.LBH589 inhibited cell proliferation of SK-NEP-1 and G401 cells in a dose-dependent manner. Annexin V, TUNEL and Hochest 33342 staining analysis showed that LBH589-treated cells showed more apoptotic features compared with the control. LBH589 treatment inhibited the growth of SK-NEP-1 xenograft tumors in nude mice. Arraystar Human LncRNA Array analysis of genes and lncRNAs regulated by LBH589 identified 6653 mRNAs and 8135 lncRNAs in LBH589-treated SK-NEP-1 cells. The most enriched gene ontology terms were those involved in nucleosome assembly. KEGG pathway analysis identified cell cycle proteins, including CCNA2, CCNB2, CCND1, CCND2, CDK4, CDKN1B and HDAC2, etc. Ingenuity Pathway Analysis identified important upstream molecules: HIST2H3C, HIST1H4A, HIST1A, HIST1C, HIST1D, histone H1, histone H3, RPRM, HSP70 and MYC.LBH589 treatment caused apoptosis and inhibition of cell proliferation of SK-NEP-1and G401 cells. LBH589 had a significant effect and few side effects on SK-NEP-1 xenograft tumors. Expression profiling, and GO, KEGG and IPA analyses identified new targets and a new "network" of genes responding to LBH589 treatment in SK-NEP-1 cells. RPRM, HSP70 and MYC may be important regulators during LBH589 treatment. Our results provide new clues to the proapoptotic mechanism of LBH589. |
| first_indexed | 2024-12-23T06:55:03Z |
| format | Article |
| id | doaj.art-6577b42536fe4e59bf40ce343bbcd6ab |
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| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T06:55:03Z |
| publishDate | 2015-01-01 |
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| spelling | doaj.art-6577b42536fe4e59bf40ce343bbcd6ab2022-12-21T17:56:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01107e012656610.1371/journal.pone.0126566Molecular Mechanism of the Cell Death Induced by the Histone Deacetylase Pan Inhibitor LBH589 (Panobinostat) in Wilms Tumor Cells.Tao Yan-FangLi Zhi-HengXu Li-XiaoFang FangLu JunLi GangCao LanWang Na-NaDu Xiao-JuanSun Li-ChaoZhao Wen-LiXiao Pei-FangZhao HeSu Guang-HaoLi Yan-HongLi Yi-PingXu Yun-YunZhou Hui-TingWu YiJin Mei-FangLiu LinNi JianHu Shao-YanZhu Xue-MingFeng XingWang JianPan JianWilms tumor (WT) is an embryonic kidney cancer, for which histone acetylation might be a therapeutic target. LBH589, a novel targeted agent, suppresses histone deacetylases in many tumors. This study investigated the antitumor activity of LBH589 in SK-NEP-1 and G401 cells.SK-NEP-1 and G401 cell growth was assessed by CCK-8 and in nude mice experiments. Annexin V/propidium iodide staining followed by flow cytometry detected apoptosis in cell culture. Gene expressions of LBH589-treated tumor cells were analyzed using an Arraystar Human LncRNA Array. The Multi Experiment View cluster software analyzed the expression data. Differentially expressed genes from the cluster analyses were imported into the Ingenuity Pathway Analysis tool.LBH589 inhibited cell proliferation of SK-NEP-1 and G401 cells in a dose-dependent manner. Annexin V, TUNEL and Hochest 33342 staining analysis showed that LBH589-treated cells showed more apoptotic features compared with the control. LBH589 treatment inhibited the growth of SK-NEP-1 xenograft tumors in nude mice. Arraystar Human LncRNA Array analysis of genes and lncRNAs regulated by LBH589 identified 6653 mRNAs and 8135 lncRNAs in LBH589-treated SK-NEP-1 cells. The most enriched gene ontology terms were those involved in nucleosome assembly. KEGG pathway analysis identified cell cycle proteins, including CCNA2, CCNB2, CCND1, CCND2, CDK4, CDKN1B and HDAC2, etc. Ingenuity Pathway Analysis identified important upstream molecules: HIST2H3C, HIST1H4A, HIST1A, HIST1C, HIST1D, histone H1, histone H3, RPRM, HSP70 and MYC.LBH589 treatment caused apoptosis and inhibition of cell proliferation of SK-NEP-1and G401 cells. LBH589 had a significant effect and few side effects on SK-NEP-1 xenograft tumors. Expression profiling, and GO, KEGG and IPA analyses identified new targets and a new "network" of genes responding to LBH589 treatment in SK-NEP-1 cells. RPRM, HSP70 and MYC may be important regulators during LBH589 treatment. Our results provide new clues to the proapoptotic mechanism of LBH589.http://europepmc.org/articles/PMC4503685?pdf=render |
| spellingShingle | Tao Yan-Fang Li Zhi-Heng Xu Li-Xiao Fang Fang Lu Jun Li Gang Cao Lan Wang Na-Na Du Xiao-Juan Sun Li-Chao Zhao Wen-Li Xiao Pei-Fang Zhao He Su Guang-Hao Li Yan-Hong Li Yi-Ping Xu Yun-Yun Zhou Hui-Ting Wu Yi Jin Mei-Fang Liu Lin Ni Jian Hu Shao-Yan Zhu Xue-Ming Feng Xing Wang Jian Pan Jian Molecular Mechanism of the Cell Death Induced by the Histone Deacetylase Pan Inhibitor LBH589 (Panobinostat) in Wilms Tumor Cells. PLoS ONE |
| title | Molecular Mechanism of the Cell Death Induced by the Histone Deacetylase Pan Inhibitor LBH589 (Panobinostat) in Wilms Tumor Cells. |
| title_full | Molecular Mechanism of the Cell Death Induced by the Histone Deacetylase Pan Inhibitor LBH589 (Panobinostat) in Wilms Tumor Cells. |
| title_fullStr | Molecular Mechanism of the Cell Death Induced by the Histone Deacetylase Pan Inhibitor LBH589 (Panobinostat) in Wilms Tumor Cells. |
| title_full_unstemmed | Molecular Mechanism of the Cell Death Induced by the Histone Deacetylase Pan Inhibitor LBH589 (Panobinostat) in Wilms Tumor Cells. |
| title_short | Molecular Mechanism of the Cell Death Induced by the Histone Deacetylase Pan Inhibitor LBH589 (Panobinostat) in Wilms Tumor Cells. |
| title_sort | molecular mechanism of the cell death induced by the histone deacetylase pan inhibitor lbh589 panobinostat in wilms tumor cells |
| url | http://europepmc.org/articles/PMC4503685?pdf=render |
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