FLT3-specific curcumin micelles enhance activity of curcumin on FLT3-ITD overexpressing MV4-11 leukemic cells

• Main Authors: Singkome Tima, Siriporn Okonogi, Chadarat Ampasavate, Cory Berkland, Songyot Anuchapreeda
• Format: Journal
• Published: 2019
• Subjects: Chemistry; Pharmacology, Toxicology and Pharmaceutics
• Online Access: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85060604345&origin=inward; http://cmuir.cmu.ac.th/jspui/handle/6653943832/63615
• Institution: Chiang Mai University

© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. Curcumin, a major active compound in the turmeric rhizome, has many biological properties, especially anti-leukemia activity. The overexpression of FMS-like tyrosine kinase 3 protein with internal tandem duplication (FLT3-ITD) mutation protein was related to the poor prognosis and disease progression of leukemia. In this study, the cytotoxicity and inhibitory effect of curcumin on cell cycle of FLT3-ITD overexpressing MV4-11 leukemic cells were evaluated. Moreover, curcumin polymeric micelles conjugated with FLT3-specific peptide (FLT3-Cur-micelles) were prepared using a film hydration method to increase curcumin solubility and the inhibitory effect on MV4-11 cells was evaluated. Cytotoxicity and cell cycle analysis were performed using an MTT assay and flow cytometry, respectively. Physical properties of FLT3-Cur-micelles, including particle size, size distribution, morphology, and entrapment efficiency (EE), were evaluated. Cellular uptake of the micelles on MV4-11 cells was determined by flow cytometry and fluorescence microscopy. FLT3-Cur-micelles were observed with size less than 50 nm and high EE of >75%. In addition, FLT3-Cur-micelles demonstrated excellent internalization and increased curcumin accumulation in leukemic cells when compared to free curcumin. Furthermore, FLT3-Cur-micelles exhibited a strong cytotoxic effect on MV4-11 cells with IC 50 value of 1.1 µM, whereas the blank micelles showed no effect. Furthermore, FLT3-Cur-micelles showed no significant effect on normal human PBMCs with IC 50 value >25 µM. In summary, FLT3-Cur-micelles are a promising nanocarrier system for enhancing anti-leukemic activity of curcumin and suitable for further preclinical studies.