Send to

Choose Destination
Anticancer Drugs. 2018 Jan;29(1):61-74. doi: 10.1097/CAD.0000000000000568.

Histone deacetylase inhibitor BG45-mediated HO-1 expression induces apoptosis of multiple myeloma cells by the JAK2/STAT3 pathway.

Tang S1,2,3, Cheng B1,2, Zhe N1,2,3, Ma D4,1,3, Xu J5, Li X1,2,3, Guo Y1,2,3, Wu W1,2,3, Wang J4,1,3.

Author information

Guizhou Province Hematopoietic Stem Cell Transplantation Center, Affiliated Hospital of Guizhou Medical University.
School of Clinical Medicine, Guizhou Medical University, Guizhou.
Key Laboratory of Hematological Disease Diagnostic, Treat Centre of Guizhou Province, Guiyang.
Department of Hematology.
Department of Internal Medicine, the People's Hospital of Anshun, Anshun, China.


Multiple myeloma (MM) is a hematological malignancy that is characterized by the clonal expansion of plasma cells in the bone marrow. Histone deacetylases (HDACs) represent a new type of molecular targeted therapy for different types of cancers and promising targets for myeloma therapy. We showed that HDAC3 mRNA and protein levels of CD138 mononuclear cells from MM patients were higher than those in healthy donors. Therefore, we investigated the effects of a novel class I HDAC inhibitor BG45 on MM cells in vitro. BG45 downmodulated heme oxygenase 1 (HO-1) when class I HDACs decreased in MM cells. HO-1 is a target for the treatment of MM. Moreover, BG45 induced hyperacetylation of histone H3 and inhibited the growth, especially the apoptosis of MM cell lines. Treatment with BG45 induced apoptosis by downregulating bcl-2 and Bcl-xl, upregulating Bax and other antiapoptotic proteins and activating poly(ADP-ribose)polymerase, and decreasing protein levels of p-JAK2 and p-STAT3. These effects were partly blocked by HO-1. Correspondingly, BG45 led to an accumulation in the G0/G1 phase, accompanied by decreased levels of CDK4 and phospho-retinoblastoma protein, an increased level of p21, and a moderately reduced level of CDK2. Clinical use of single agents was limited because of toxic side effects and drug resistance. However, combining BG45 with lenalidomide exerted synergistic effects. In conclusion, we verified the potent antimyeloma activity of this novel HDAC inhibitor and that the combination of BG45 and lenalidomide is a new method for MM treatment. Thus, BG45 may be applicable to the treatment of MM and other hematological malignancies.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wolters Kluwer
Loading ...
Support Center