Changes in the Expression of TBP-2 in Response to Histone Deacetylase Inhibitor Treatment in Human Endometrial Cells

Abstract

Histone deacetylase inhibitors (HDACi) induce apoptosis preferentially in cancer cells by caspase pathway activation and reactive oxygen species (ROS) accumulation. Suberoylanilide hydroxamic acid (SAHA), a HDACi, increases apoptosis via altering intracellular oxidative stress through thioredoxin (TRX) and TRX binding protein-2 (TBP-2). Because ROS accumulation, as well as the redox status determined by TBP-2 and TRX, are suggested as possible mechanisms for endometriosis, we queried whether SAHA induces apoptosis of human endometrial cells via the TRX–TBP-2 system in endometriosis. Eutopic endometrium from participants without endometriosis, and ectopic endometrium from patients with endometriosis, was obtained surgically. Human endometrial stromal cells (HESCs) and Ishikawa cells were treated with SAHA and cell proliferation was assessed using the CCK-8 assay. Real-time PCR and Western blotting were used to quantify TRX and TBP-2 mRNA and protein expression. After inducing oxidative stress, SAHA was applied. Short-interfering TRX (SiTRX) transfection was performed to see the changes after TRX inhibition. The mRNA and protein expression of TBP-2 was increased with SAHA concentrations in HESCs significantly. The mRNA TBP-2 expression was decreased after oxidative stress, upregulated by adding 2.5 μM of SAHA. The TRX/TBP-2 ratio decreased, apoptosis increased significantly, and SiTRX transfection decreased with SAHA. In conclusion, SAHA induces apoptosis by modulating the TRX/TBP-2 system, suggesting its potential as a therapeutic agent for endometriosis.

POLR2J expression promotes glioblastoma malignancy by regulating oxidative stress and the STAT3 signaling pathway

“…These findings suggest a correlation between POLR2J and UPR in GBM, where POLR2J knockdown enhances UPR activation. Given that HDAC inhibitors induce apoptosis in cancer cells through ROS accumulation [39], POLR2J silencing could potentially enhance the anti-cancer activity of vorinostat by increasing ROS accumulation, presenting a novel chemo-sensitization strategy for vorinostat treatment in GBM.…”

POLR2J is a potential biomarker for abnormal tumor progression, vorinostat sensitization, immune infiltration, and prognosis of glioblastoma multiform

“…These data indicated that POLR2J was correlated with oxidoreductase activity and UPR in GBM, and POLR2J knockdown enhanced ROS-UPR in GBM cells. HDAC inhibitors induce apoptosis in cancer cells by ROS accumulation [39]. Thus, POLR2J silence might enhance the anti-cancer activity of vorinostat by increasing ROS accumulation, and POLR2J silence might be a novel chemosensitization strategy for vorinostat treatment against GBM.…”

The Impact of Histone Modifications in Endometriosis Highlights New Therapeutic Opportunities

“…Kim et al treated eutopic and ectopic human endometrial stromal cells with suberoylanilide hydroxamic acid and concluded that the aforementioned HDACI significantly upregulated the Thioredoxin (TRX) Binding Protein-2 (TBP-2) mRNA and protein expression, led to the reduction of the TRX/TBP-2 ratio, induced apoptosis, and halted the transfection of short-interfering TRX [55]. Moreover, Zheng et al first induced endometriosis in Krüppel-like factor 11 (Klf11) -/-mice through surgical autologous uterine tissue implantation and treated them with suberoylanilide hydroxamic acid, but did not observe any changes in collagen 1A1 expression and, consequently, the extent of fibrosis.…”