Effect of BCLAF1 on HDAC inhibitor LMK-235-mediated apoptosis of diffuse large B cell lymphoma cells and its mechanism

  • Cancer Biol Ther. 2018;19(9):825-834. doi: 10.1080/15384047.2018.1472188.
Xinyao Li  1  2  3 ,  Zhengchang He  1  2  3 ,  Bingqing Cheng  4  2  3 ,  Qin Fang  4  5 ,  Dan Ma  1  2  3 ,  Tingting Lu  1  2  3 ,  Danna Wei  1  2  3 ,  Xingyi Kuang  1  2  3 ,  Sishi Tang  1  2  3 ,  Jie Xiong  1  2  3 ,  Jishi Wang  1  2  3
Affiliations
  • 1. a Guizhou Medical University , Guiyang , Guizhou , China.
  • 2. d Guizhou Province Laboratory of Haematopoietic Stem Cell Transplantation Center , Guiyang , Guizhou , China.
  • 3. e Department of Hematology , Affiliated Hospital of Guizhou Medical University , Guiyang , Guizhou , China.
  • 4. b Department of Pharmacy , Guizhou Medical University , Guiyang , Guizhou , China.
  • 5. c Department of Pharmacy , Affiliated BaiYun Hospital of Guizhou Medical University , Guiyang , Guizhou , China.
PMID: 29969367 DOI: 10.1080/15384047.2018.1472188
Abstract

Diffuse large B-cell lymphoma (DLBCL) is the most common type of adult lymphoma. It is a group of malignant tumors with a large number of clinical manifestations and prognoses. Therefore, it is necessary to explore its unknown potential therapeutic targets. Histone deacetylase inhibitor (HDACi) is a novel drug for the treatment of DLBCL, however pan-HDACis cannot be ignored because of their clinical efficacy. By contrast, specific HDACi is well-tolerated, and LMK-235 is a novel HDACi that is a specific inhibitor of HDAC4 and HDAC5. In this study, we investigated the up-regulation of BCLAF1 through NF-κB signaling pathways in LMK-235, mediating the Apoptosis of two diffuse large B-cell lymphoma cell lines, OCI-LY10 and OCI-LY3. Further studies showed that BCLAF1 expression was increased in DLBCL cells after treatment with the NF-κB Inhibitor Bay11-7082. The combination of Bay11-7082 and siRNA si-HDAC4 significantly increased BCLAF1 expression and further increased Apoptosis. These results indicate that BCLAF1 plays an important role in LMK-235-mediated Apoptosis and may be a potential target for the treatment of diffuse large B-cell lymphoma.

Keywords
BCLAF1; HDAC4; LMK-235; NF-kB; apoptosis; diffuse large B cell lymphoma.
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-18998
    LMK-235
    99.61%, HDAC4/5 Inhibitor
    target: HDAC
    Research Areas: Cancer