The inhibitor of the redox activity of APE1/REF-1, APX2009, reduces the malignant phenotype of breast cancer cells

• Published in: Brazilian journal of medical and biological research Vol. 57; p. e13250
• Main Authors: Siqueira, P B, Rodrigues, M M S, Amorim, Ĺ S S de, Rodrigues, J A, Oliveira, M S, Fonseca, A S, Pires, B R B, Mencalha, A L
• Format: Journal Article
• Language: English
• Published: Brazil Associacao Brasileira de Divulgacao Cientifica (ABDC) 01.01.2024; Associação Brasileira de Divulgação Científica
• Subjects: Antimitotic agents; Antineoplastic agents; Antineoplastic Agents - pharmacology; APE1/REF-1; Apoptosis - drug effects; APX2009; BIOLOGY; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Development and progression; DNA-(Apurinic or Apyrimidinic Site) Lyase - antagonists & inhibitors; DNA-(Apurinic or Apyrimidinic Site) Lyase - metabolism; Drug therapy; Female; Humans; Invasion; MCF-7 Cells; MEDICINE, RESEARCH & EXPERIMENTAL; Migration; Oncology, Experimental; Oxidation-Reduction - drug effects; Oxidation-reduction reaction; Phenotype; Brazil; APX2009; APE1/REF-1; Breast cancer; Migration; Invasion
• ISSN: 0100-879X; 1414-431X; 1414-431X
• DOI: 10.1590/1414-431X2024e13250

Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/REF-1) is a multifunctional protein acting on cellular signaling pathways, including DNA repair and redox activities. APE1/REF-1 has emerged as a target for cancer therapy, and its role in breast cancer models would reveal new strategies for cancer therapy. APX2009 is a specific APE1/REF-1 redox inhibitor whose anticancer properties have not been described in breast cancer cells. Here, we investigated the effect of the APX2009 treatment in the breast cancer cell lines MDA-MB-231 and MCF-7. Breast cancer cell lines were cultured, and WST1 and colony formation assays were performed to evaluate cell proliferation. Annexin V-FITC/7-AAD and LDH-Glo™ assays were performed to evaluate cell death. The wound healing assay and Matrigel transwell assay were performed after APX2009 treatment to evaluate the cellular migration and invasion processes, respectively. Our findings demonstrated that APX2009 treatment decreased breast cancer cell proliferative, migratory, and invasive properties. Furthermore, it induced apoptosis in both cell lines. Our study is the first to show the effects of APX2009 treatment on apoptosis in a breast cancer cell. Therefore, this study suggested that APX2009 treatment is a promising anticancer molecule for breast cancer.