Reprogramming of erythrocyte lifespan by NFκB-TNFα naphthoquinone antagonist β-lapachone is regulated by calcium overload and CK1α.

摘要: The pathophysiology of chemotherapy-associated anemia, prevalent in at least 75% patients, remains difficult to establish. Chemotherapy-related anemia is attributed part eryptosis, and it therefore considerable interest interrogate the toxicity investigative anticancer compounds red blood cells (RBCs). Beta-lapachone (LAP), an anthraquinone extracted from bark Lapacho tree (Tabebuia avellanedae), effective against a myriad cancer cells. However, LAP RBCs unexplored. Hemoglobin leakage as surrogate for hemolysis was photometrically measured, while flow cytometry employed capture phosphatidylserine (PS) exposure with Annexin-V-FITC, calcium levels Fluo4/AM, cell size by forward scatter (FSC), oxidative stress H2DCFDA. Our results show that LAP, antitumor (10-30 µM), induces dose-dependent secondary influx extracellular space. Moreover, stimulates evident PS exposure, which associated reduced volume intracellular overload. Importantly, also revealed cytotoxicity mediated through casein kinase 1α. Altogether, this report shows, first time, possesses both hemolytic eryptotic potential necessitates careful application chemotherapy. PRACTICAL APPLICATIONS: widely consumed herbal tea origins Tabebuia avellanedae endogenous South America. one active ingredients lapacho promising potential. We cytotoxic human virtue eryptosis hemolysis, we identify molecular mechanisms. Given these two manifestations are known contribute chemotherapy-induced our study provides invaluable insights into suitability management sheds some light on possible strategies limit its undesirable side effects.