Therapeutic positioning of secretory acetylated APE1/Ref-1 requirement for suppression of tumor growth in triple-negative breast cancer in vivo

Abstract

Triple-negative breast cancer (TNBC) represents a relatively small proportion of all BCs but a relatively large proportion of BC-related death. Thus, more effective therapeutic strategies are needed for the management of TNBC. We demonstrated that the stimulation of apoptosis by the binding of secreted acetylated-apurinic apyrimidinic endonuclease 1/redox factor-1 (Ac-APE1/Ref-1) to the receptor for advanced glycation end products (RAGE) was essential for TNBC cell death in response to hyperacetylation. The aim of the present study was to assess the potential therapeutic efficacy of secretory Ac-APE1/Ref-1 in orthotopic TNBC xenografts in vivo. We found that hyperacetylation in xenografts caused secretion of Ac-APE1/Ref-1 into the blood, where the factor bound directly to RAGE in hyperacetylated tumor tissues. Hyperacetylation in the TNBC xenografts induced strong inhibition of tumor growth and development, leading to apoptotic cell death, accompanied by increased RAGE expression and generation of reactive oxygen species. Tissues exhibited markedly higher counts of apoptotic bodies, a reduced proliferation index, and reduced neovascularization compared with control tumors. Ac-APE1/Ref-1-stimulated apoptosis was markedly reduced in RAGE-knockdown tumors compared with RAGE-overexpressing tumors, even in the presence of hyperacetylation. The function of secreted Ac-APE1/Ref-1 was confirmed in other hyperacetylated TNBCs xenografts using BT-549 and MDA-MB-468 cells, demonstrating its relevance as an anti-cancer molecule.

APEX1 Expression as a Potential Diagnostic Biomarker of Clear Cell Renal Cell Carcinoma and Hepatobiliary Carcinomas

“…ELISA was conducted as previously described using an APEX1 enzyme-linked immunosorbent assay kit (Cat#MR-APE064-HS. MediRedox Inc., Daejeon, Korea), including the mouse monoclonal anti-human APEX1 antibody (Cat#LS-C392589, LifeSpan BioSciences, WA, USA) and the rabbit polyclonal anti-human APEX1 antibody (MediRedox, Daejeon, Korea) [11].…”

Low lamin A levels enhance confined cell migration and metastatic capacity in breast cancer

“…BT-549 PIDC, Primary tumor (Lasfargues and Coutinho, 1981) Basal B / Claudin low 24 h +++++ Invasive Originally thought to be non-tumorigenic and may require addition of Matrigel for growth in MFPs of nude mice (Lee et al, 2018;Thompson et al, 1992). Infrequently used in vivo for tumor growth assays (MFP and SC injection) and for lung metastasis from circulation assays (Banerjee et al, 2011;Chen et al, 2017;Hahn et al, 1999;Jiang et al, 2020;Murthy et al, 1995;Tate et al, 2012;Walsh et al, 2017;Yoon et al, 2012 (Thompson et al, 1992) and rarely metastatic in nude mice (Clarke, 1996;Ozzello and Sordat, 1980;Shafie and Liotta, 1980), but some metastasis has been documented in NSG mice (Iorns et al, 2012).…”

Inhibiting Arginine Methylation as a Tool to Investigate Cross-Talk with Methylation and Acetylation Post-Translational Modifications in a Glioblastoma Cell Line

“…Second, the present work relies on antibody specificity to draw the conclusion that ADMA cross-talks with SDMA and Lys acetylation. Although the α-ADMA, α-SDMA and α-Lys acetylation antibodies that we have used are state-of-the art in the field [26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46], mass spectrometry-based proteomics approaches would complement our experiments and enable the identification of the proteins and mechanisms involved in PTM cross-talks. In particular, approaches to labelling Arg residues modified by methylation with 14 C and 13 CD 3 have been developed [47,48], and would prove very useful to identify the specific proteins undergoing methylation in further investigations of ADMA–SDMA cross-talk.…”