Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The Synergistic Effect of APE1/Ref-1 and Aspirin Enhances PEO14 Ovarian Cancer Cell Apoptosis via Parp Cleavage

Hao Jin
,
Yu Ran Lee
ORCID logo ,
Sungmin Kim
,
Eun-Ok Lee
,
Hee Kyoung Joo
,
Heon Jong Yoo
,
Cuk-Seong Kim
ORCID logo ,
Byeong Hwa Jeon
* ORCID logo
Version 1 : Received: 2 February 2024 / Approved: 2 February 2024 / Online: 2 February 2024 (09:29:00 CET)

How to cite: Jin, H.; Lee, Y.R.; Kim, S.; Lee, E.; Joo, H.K.; Yoo, H.J.; Kim, C.; Jeon, B.H. The Synergistic Effect of APE1/Ref-1 and Aspirin Enhances PEO14 Ovarian Cancer Cell Apoptosis via Parp Cleavage. Preprints 2024, 2024020123. https://doi.org/10.20944/preprints202402.0123.v1 Jin, H.; Lee, Y.R.; Kim, S.; Lee, E.; Joo, H.K.; Yoo, H.J.; Kim, C.; Jeon, B.H. The Synergistic Effect of APE1/Ref-1 and Aspirin Enhances PEO14 Ovarian Cancer Cell Apoptosis via Parp Cleavage. Preprints 2024, 2024020123. https://doi.org/10.20944/preprints202402.0123.v1

Abstract

Ovarian cancer poses a significant therapeutic challenge owing to the lack of specific targets for treatment. New treatment strategies are needed to improve patient outcomes and reduce the toxicity of existing therapies. This study aimed to investigate the synergistic effects of recombi-nant human apurinic/apyrimidinic endonuclease 1/redox factor 1 (rhAPE1/Ref-1) and aspirin on PEO14 and CAOV-3 ovarian cancer cells and human umbilical vein endothelial cells (HUVECs). Specifically, this study examined the mechanisms underlying the effect of rhAPE1/Ref-1 and as-pirin on cell death and the associated pathways. Cell viability was assessed using the MTT assay, and flow cytometry analysis and caspase-3/7 activity assays were conducted to determine apop-tosis. Western blotting was performed to evaluate the cleavage of poly(ADP-ribose) polymerase (PARP). Exposure to aspirin (3 mM) for 24 h did not affect cell viability in PEO14. Co-incubation of aspirin with rhAPE1/Ref-1 in PEO14 cells led to rhAPE1/Ref-1 acetylation and intracellular hyperacetylation. Co-treatment with aspirin (3 mM) and rhAPE1/Ref-1 induced a rhAPE1/Ref-1 concentration-dependent increase in cell death, particularly in PEO14 cells, as well as apoptosis, caspase-3/7 activation, and PARP cleavage. Furthermore, this combination treatment significantly increased paclitaxel-induced PEO14 cell death. Therefore, co-administration with rhAPE1/Ref-1 and aspirin is a potential strategy for ovarian cancer treatment.

Keywords

ovarian cancer; APE1/Ref-1; aspirin; PEO14; apoptosis; paclitaxel

Subject

Medicine and Pharmacology, Medicine and Pharmacology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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