Iguratimod-encapsulating PLGA-NPs induce human multiple myeloma cell death via reactive oxygen species and Caspase-dependent signalling

• Published in: International immunopharmacology Vol. 95; p. 107532
• Main Authors: Wang, Faming, Younis, Muhammad, Luo, Yao, Zhang, Le, Yuan, Liudi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2021; Elsevier BV
• Subjects: Animals; Anticancer properties; Antineoplastic Agents - administration & dosage; Apoptosis; Apoptosis - drug effects; Bax protein; Caspase 3 - metabolism; Caspase 9 - metabolism; Caspase signalling pathway; Caspase-3; Caspase-9; Cell cycle; Cell Cycle Checkpoints - drug effects; Cell death; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Cholecystokinin; Chromones - administration & dosage; Clinical trials; Cytochrome; Cytochrome c; Cytochromes; Encapsulation; Fluorescent indicators; Glycolic acid; Humans; Iguratimod; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Multiple myeloma; Multiple Myeloma - drug therapy; Multiple Myeloma - metabolism; Nanoparticles; Nanoparticles - administration & dosage; PLGA; Polylactic Acid-Polyglycolic Acid Copolymer - administration & dosage; Polylactide-co-glycolide; Reactive oxygen species; Reactive Oxygen Species - metabolism; Signal transduction; Signal Transduction - drug effects; Signaling; Sulfonamides - administration & dosage; Survival; Tumors; Caspase signalling pathway; PLGA; Iguratimod; Multiple myeloma
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2021.107532

•PLGA nanoparticles enhance IGU anti-tumour efficacy.•IGU-PLGA-NPs promote apoptosis and increase ROS levels in MM cells to inhibit cell proliferation and cell cycle progression.•IGU-PLGA-NPs induced MM apoptosis by activating the Caspase-dependent signalling pathway.•IGU-PLGA-NPs significantly inhibited the growth and stemness of CD138-CD34-MM CSCs. Human multiple myeloma (MM) is a currently incurable haematopoietic malignancies. Our research investigate the anti-tumour effect of iguratimod (IGU) encapsulated in poly(lactic-co-glycolic acid) PLGA nanoparticles (IGU-PLGA-NPs) on MM cells in vitro and in vivo. A significant inhibitory effect of IGU-PLGA-NPs on MM cancer cells and MM CSCs was demonstrated by the Cell Counting Kit-8 (CCK-8) assay. Treatment with IGU-PLGA-NPs induced significant cell cycle arrest at G1 in MM cells and reduced tumour colony formation in MM CSCs. Mechanistically, IGU-PLGA-NPs increase apoptosis in MM cells by activating Caspase-dependent signalling pathway to increase the levels of bax, cytochrome c (cyt-c), caspase-9 and caspase-3 proteins. Moreover, IGU-PLGA-NPs effectively increase ROS production assayed using a DCFH-DA fluorescent probe in MM cells. The data indicate that IGU-PLGA-NPs induce a significant reduction in the tumour volume and a marked increase in the survival rate in a mouse model of multiple myeloma. Overall, our findings indicate that IGU-PLGA-NPs are a potential therapeutic strategy that may contribute to the therapy of MM and elimination of MM CSCs in future clinical trials.