Quercetin: Silent Retarder of Fatty Acid Oxidation in Breast Cancer Metastasis Through Steering of Mitochondrial CPT1

Autor: Achintya Saha, Rabindranath Majumder, Sutapa Som Chaudhury, Bhuban Ruidas, Tapas Kumar Sur, Koel Sinha, Pramita Sharma, Chitrangada Das Mukhopadhyay, Sovonlal Bhowmick
Rok vydání: 2021
Předmět:
DOI: 10.21203/rs.3.rs-849234/v1
Popis: Recent evidence concreted that maximum energy in metastatic breast cancer progression is supplied by fatty acid oxidation (FAO) governed by a rate-limiting enzyme, carnitine palmitoyltransferase 1 (CPT1). Therefore, active limitation of FAO could be an emerging aspect to inhibit breast cancer progression. Herein, for the first time we have introduced Quercetin (QT) from a non-dietary source (Mikania micrantha Kunth) to seize the FAO in triple-negative breast cancer cells (TNBC) through an active targeting of CPT1. Apart from successive molecular quantification, QT has resulted a significant reduction in the intracellular mitochondrial respiration and glycolytic function limiting extensive ATP production. In turn, QT has elevated the reactive oxygen species (ROS) and depleted antioxidant level to induce anti-metastatic and cell apoptosis activities. Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) investigated the FAO associated gene expression resulting significant depletion in FAO which were further confirmed through the successful in-silico molecular docking prediction for active binding potentiality of QT to CPT1. Subsequently, QT has shown an excellent in-vivo antitumor activities through the altered lipid profile and oxidative stress healing capabilities in female breast cancer BALB/c mice model. Therefore, all the obtained data significantly grounded the fact that QT could be a promising metabolism-targeted breast cancer therapeutics.
Databáze: OpenAIRE