Caveolin-1 contributes to realgar nanoparticle therapy in human chronic myelogenous leukemia K562 cells

• Published in: International journal of nanomedicine Vol. 11; pp. 5823 - 5835
• Main Authors: Shi, Dan, Liu, Yan, Xi, Ronggang, Zou, Wei, Wu, Lijun, Zhang, Zhiran, Liu, Zhongyang, Qu, Chao, Xu, Baoli, Wang, Xiaobo
• Format: Journal Article
• Language: English
• Published: New Zealand Taylor & Francis Ltd 01.01.2016; Dove Medical Press
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; Arsenicals - chemistry; Arsenicals - pharmacology; Autophagy; Autophagy - drug effects; Bcr-Abl fusion protein; Blood; Cancer; Caveolin 1 - metabolism; Caveolin-1; Cell cycle; Cell Differentiation - drug effects; Cell growth; Cell Proliferation - drug effects; Fusion Proteins, bcr-abl - metabolism; Hematology; Humans; Immunoglobulins; K562 Cells - drug effects; Kinases; Laboratory animals; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - therapeutic use; Original Research; Particle size; Pharmacy; Phosphatidylinositol 3-Kinases - metabolism; Proteins; Rats, Sprague-Dawley; realgar nanoparticles; Stem cells; Sulfides - chemistry; Sulfides - pharmacology; TOR Serine-Threonine Kinases - metabolism; Beijing China; United States > US; China; caveolin-1; apoptosis; autophagy; Bcr-Abl fusion protein; realgar nanoparticles
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/ijn.s115158

Chronic myelogenous leukemia (CML) is characterized by the t(9;22) (q34;q11)-associated fusion gene, which is an essential element of clinical diagnosis. As a traditional Chinese medicine, realgar has been widely used for the treatment of various diseases for >1,500 years. Inspired by nano-drug, realgar nanoparticles (NPs) have been prepared with an average particle size of <100 nm in a previous work. Compared with coarse realgar, the realgar NPs have higher bioavailability. As a principal constituent protein of caveolae, caveolin-1 (Cav-1) participates in regulating various cellular physiological and pathological processes including tumorigenesis and tumor development. In previous studies, it was found that realgar NPs can inhibit several types of tumor cell proliferation. However, the therapeutic effect of realgar NPs on CML has not been fully elucidated. In the present paper, it was demonstrated that realgar NPs can inhibit the proliferation of K562 cells and degrade Bcr-Abl fusion protein effectively. Both apoptosis and autophagy were activated in a dose-dependent manner in realgar NPs treated cells, and the induction of autophagy was associated with class I phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathway. Morphological analysis indicated that realgar NPs induced differentiation effectively in CML cells. Furthermore, it was identified that Cav-1 might play a crucial role in realgar NP therapy. In order to study the effects of Cav-1 on K562 cells during realgar NP treatment, a Cav-1 overexpression cell model was established by using transient transfection. The results indicated that Cav-1 overexpression inhibited K562 cell proliferation, promoted endogenic autophagy, and increased the sensitivity of K562 cells to realgar NPs. Therefore, the results demonstrated that realgar NPs degraded Bcr-Abl oncoprotein, while the underlying mechanism might be related to apoptosis and autophagy, and Cav-1 might be considered as a potential target for clinical comprehensive therapy of CML.