In vitro assessment of the anticancer activity of quinaldic acid against human breast cancer cells (MCF-7)

Abstract

Breast carcinoma represents one of the most frequently diagnosed types of cancer among women throughout the world. The drawbacks of current chemotherapy drugs include adverse side effects, development of drug resistance and lack of selectivity for cancer cells. This highlights the need to develop novel, highly active antitumor compounds with improved therapeutic efficacy and safety. Quinaldic acid (QA) is a biologically active compound that has shown antiproliferative activity in some cancer models, but its anticancer activity against breast carcinoma has not been sufficiently investigated. The present research aims to study the anticancer activity of QA in MCF-7 cells (human breast adenocarcinoma cells). Antiproliferative activity was determined with the MTT assay, with cisplatin used as the standard drug. The generation of reactive oxygen species (ROS), polarization of mitochondrial membrane and nuclear morphology were studied to evaluate the possible mechanisms of action of QA. The apoptosis inducing potential and quantitative estimation of apoptotic cells were identified with AO/EtBr staining and flow cytometry respectively. QA showed dose-dependent antiproliferative activity against MCF-7 cells along with considerably lower cytotoxicity in normal L929 cells, which indicates its higher cytotoxicity against carcinoma cells. The QA treatment resulted in a significant increase in ROS production and depolarization of the mitochondrial membrane, which highlights the effective role of the intrinsic apoptosis pathway. DAPI and AO/EtBr staining revealed prominent apoptotic features and a higher percentage of apoptotic cells. Flow cytometry viable cell count reduction and an increase in early and late apoptotic cell counts. QA showed greatest and selective anticancer activity against MCF-7 by inducing ROS-mediated mitochondrial dysfunction and apoptosis, while exhibiting comparatively low cytotoxicity toward normal fibroblast cells.