title: Dendrosomal curcumin nanoformulation downregulates pluripotency genes via miR-145 activation in U87MG glioblastoma cells.
abstract: Glioblastoma is an invasive tumor of the central nervous system. Tumor recurrence resulting from ineffective current treatments, mainly due to the blood-brain barrier, highlights the need for innovative therapeutic alternatives. The recent availability of nanotechnology represents a novel targeted strategy in cancer therapy. Natural products have received considerable attention for cancer therapy because of general lower side effects. Curcumin is a new candidate for anticancer treatment, but its low bioavailability and water solubility represent the main disadvantages of its use. Here, curcumin was efficiently encapsulated in a nontoxic nanocarrier, termed dendrosome, to overcome these problems. Dendrosomal curcumin was prepared as 142 nm spherical structures with constant physical and chemical stability. The inhibitory role of dendrosomal curcumin on the proliferation of U87MG cells, a cellular model of glioblastoma, was evaluated by considering master genes of pluripotency and regulatory miRNA (microribonucleic acid). Methylthiazol tetrazolium assay and flow cytometry were used to detect the antiproliferative effects of dendrosomal curcumin. Annexin-V-FLUOS and caspase assay were used to quantify apoptosis. Real-time polymerase chain reaction was used to analyze the expression of OCT4 (octamer binding protein 4) gene variants (OCT4A, OCT4B, and OCT4B1), SOX-2 (SRY [sex determining region Y]-box 2), Nanog, and miR-145. Dendrosomal curcumin efficiently suppresses U87MG cells growth with no cytotoxicity related to dendrosome. Additionally, the accumulation of cells in the SubG1 phase was observed in a time- and dose-dependent manner as well as higher rates of apoptosis after dendrosomal curcumin treatment. Conversely, nonneoplastic cells were not affected by this formulation. Dendrosomal curcumin significantly decreased the relative expression of OCT4A, OCT4B1, SOX-2, and Nanog along with noticeable overexpression of miR-145 as the upstream regulator. This suggests that dendrosomal curcumin reduces the proliferation of U87MG cells through the downregulation of OCT4 (octamer binding protein 4) variants and SOX-2 (SRY [sex determining region Y]-box 2) in an miR-145-dependent manner.
authors: Department of Genetics, Tarbiat Modares University, Tehran, Iran.
authors: Maryam
authors: M
authors: Tahmasebi Mirgani
authors: Department of Chemistry, University of Florence, Sesto Fiorentino, Italy.
authors: Benedetta
authors: B
authors: Isacchi
authors: Department of Genetics, Tarbiat Modares University, Tehran, Iran.
authors: Majid
authors: M
authors: Sadeghizadeh
authors: Department of Experimental and Clinical Medicine, University of Florence, Italy.
authors: Fabio
authors: F
authors: Marra
authors: Department of Chemistry, University of Florence, Sesto Fiorentino, Italy.
authors: Anna Rita
authors: AR
authors: Bilia
authors: Department of Genetics, Tarbiat Modares University, Tehran, Iran.
authors: Seyed Javad
authors: SJ
authors: Mowla
authors: Department of Resin and Additives, Institute for Color Science and Technology, Tehran, Iran.
authors: Farhood
authors: F
authors: Najafi
authors: Department of Biology, University of Tabriz, Tabriz, Iran.
authors: Esmael
authors: E
authors: Babaei
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D003474:Curcumin / Q000008:administration & dosage / Q000627:therapeutic use*; D015536:Down-Regulation / Q000187:drug effects; D004337:Drug Carriers; D004355:Drug Stability; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D058990:Molecular Targeted Therapy; D053769:Nanocapsules / Q000737:chemistry / Q000627:therapeutic use* / Q000648:ultrastructure; D000071317:Nanog Homeobox Protein; D050997:Nanomedicine; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D018398:Homeodomain Proteins; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; C486780:NANOG protein, human; D053769:Nanocapsules; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors; D020169:Caspases; D003474:Curcumin
keywords: dendrosomal curcumin; glioblastoma; miRNA; pluripotency gene