BAY 87‑2243 sensitizes hepatocellular carcinoma Hep3B cells to histone deacetylase inhibitors treatment via GSK‑3β activation

Abstract

Hepatocellular carcinoma (HCC) is associated with some of the highest cancer-associated mortality rates. Histone deacetylase (HDAC) inhibitors anti-HCC activities have been shown to promote Snail-induced metastasis. In the present study, it was shown that BAY 87-2243, a hypoxia-inducible transcription factor-1α inhibitor, could enhance the anti-HCC effects of HDAC inhibitors, including trichostatin A and vorinostat. In addition, BAY 87-2243 plus HDAC inhibitors exhibited synergistic cytotoxicity and induced significant cell death in Hep3B cells. Additionally, BAY 87-2243 combined with HDAC inhibitors-treated Hep3B cells formed fewer and smaller colonies as compared with either the control or single agent-treated cells. Furthermore, glycogen synthase kinase-3β might be involved in the enhanced cell death induced by BAY 87-2243 plus HDAC inhibitors. The present data also indicated that BAY 87-2243 combined with HDAC inhibitors could suppress the migration of Hep3B cells, and BAY 87-2243 could reverse the HDAC inhibitor-induced Snail activation in Hep3B cells. In conclusion, BAY 87-2243 combined with HDAC inhibitors might be an attractive chemotherapy strategy for HCC therapy.

LPCAT1 overexpression promotes the progression of hepatocellular carcinoma

“…The molecular formulas of such drugs are presented in Additional file 12 : Figure S10. Surprisingly, the anti-HCC effects of LY-294002 [ 41 ], trichostatin A [ 42 ], sirolimus [ 43 ], vorinostat [ 44 ], and harmine [ 45 ] have been demonstrated by in vitro or in vivo experiments.…”

“…The molecular formulas of such drugs are presented in Additional file 12: Figure S10. Surprisingly, the anti-HCC effects of LY-294002 [41], trichostatin A [42], sirolimus [43], Fig. 7 The genetic regulatory network of LPCAT1's differentially co-expressed genes in hepatocellular carcinoma.…”

Reactive Oxygen Species (ROS) Regulates Different Types of Cell Death by Acting as a Rheostat

“…Furthermore RIPK1, MLKL, and GPx4 knockdown prevented loss of cell viability; in contrast, GPx4 overexpression inhibited the BAY-induced increase in intracellular ROS and lipid peroxidation and inhibited reduction in cell viability [ 136 ]. Interestingly, in hepatoma cell line Hep3B, treatment with BAY 87-2243 had antiproliferative effects and induced cell death by apoptosis; it was also observed that both effects were enhanced when BAY 87-2243 was combined with histone deacetylase inhibitors [ 137 ]. This mitochondrial complex-1 inhibitor was the object of a phase I clinical trial ( NCT01297530 ).…”

Long non-coding RNA DLGAP1-AS1 facilitates tumorigenesis and epithelial–mesenchymal transition in hepatocellular carcinoma via the feedback loop of miR-26a/b-5p/IL-6/JAK2/STAT3 and Wnt/β-catenin pathway

“…On the basis of previous description, western blot was carried out 16 . Following primary antibodies were bought from Abcam (Cambridge, UK): anti-E-cadherin (ab1416), anti-N-cadherin (ab18203), anti-Vimentin (ab8978), anti-Twist (ab175430), anti-JAK2 (ab108596), anti-p-JAK2 (ab32101), anti-STAT3 (ab119352), anti-p-STAT3 (ab32143), anti-CDK8 (ab224828), anti-LRP6 (ab75358), anti-β-catenin (ab32572), anti-p-β-catenin (ab27798), anti-Cyclin D1 (ab16663), anti-c-Myc (ab32072), anti-MMP9 (ab38898) and anti-GAPDH (ab8245).…”