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

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.

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

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.

Investigation of the mutagenic and genotoxic activities of LLL-3, a STAT3 inhibitor.

LLL-3, an anthracene derived compound, has been shown to be a promising therapeutic agent for the treatment of some kinds of cancer such as chronic myeloid leukemia and glioblastoma. However, no data regarding the toxic properties of this compound have yet been described in the literature. The present work aimed to investigate the mutagenic and genotoxic activities of LLL-3 using the TA97, TA98, TA100, TA102 and TA104 Salmonella/microsome strains for the Ames test and the micronucleus assay with the mouse macrophage cell line RAW 264.7. The findings showed that LLL-3, at doses of 0.001, 0.01, 0.1, 1.0 and 10.0 µg/plate, did not induce mutagenic activity in the Salmonella strains used under the conditions tested, and nor did it present genotoxicity in RAW 264.7 cells, at 10.0, 100.0 and 1000.0 µg/mL doses. Moreover, it is important to point out that the mitotic index of the cells decreased after exposure to LLL-3 under the same conditions tested, which may suggest some cytostatic effect, since this compound acts by inhibiting STAT3. Since most drugs used in the treatment of cancer present mutagenic activity as an adverse effect, these results suggest that LLL-3 is a promising drug for cancer therapy.

Accurate monitoring of promoter gene methylation with high-resolution melting polymerase chain reaction using the ABCB1 gene as a model.

Multidrug resistance is the major cause of cancer chemotherapy failure. This phenotype is mainly due to the overexpression of the human ABCB1 gene. Several studies have shown that the transcriptional regulation of this gene is complex. Yet, the impact of this transcriptional regulation has not been well studied in a clinical setting. The acquired expression of ABCB1 is associated with the genomic instability of cancer cells. This includes the occurrence of mutational events that alter chromatin structures through epigenetic modifications such as promoter methylation. Therefore, it is important to introduce new clinical methods to monitor the methylation status of ABCB1 and determine its association with gene expression in order to be able to predict response to therapies. The high-resolution melting (HRM) method has emerged as a highly accurate and sensitive method to quantify methylation status at specific sites of DNA. Here, we established HRM parameters to evaluate the promoter methylation status of the ABCB1 gene. Our study is the first to standardize the HRM dissociation curve to evaluate ABCB1 gene methylation. The association between ABCB1 methylation status and gene expression in established cancer cell lines shows that this method is accurate and reliable.