Dendrosomal curcumin nanoformulation downregulates pluripotency genes via miR-145 activation in U87MG glioblastoma cells

Maryam Tahmasebi Mirgani,1 Benedetta Isacchi,2 Majid Sadeghizadeh,1,* Fabio Marra,3 Anna Rita Bilia,2,* Seyed Javad Mowla,1 Farhood Najafi,4 Esmael Babaei51Department of Genetics, Tarbiat Modares University, Tehran, Iran; 2Department of Chemistry, University of Florence, Sesto Fiorentino, Italy; 3De...

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Main Authors: Tahmasebi Mirgani M, Isacchi B, Sadeghizadeh M, Marra F, Bilia AR, Mowla SJ, Najafi F, Babaei E
Format: Article
Language:English
Published: Dove Medical Press 2014-01-01
Series:International Journal of Nanomedicine
Online Access:http://www.dovepress.com/dendrosomal-curcumin-nanoformulation-downregulates-pluripotency-genes--a15489
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author Tahmasebi Mirgani M
Isacchi B
Sadeghizadeh M
Marra F
Bilia AR
Mowla SJ
Najafi F
Babaei E
author_facet Tahmasebi Mirgani M
Isacchi B
Sadeghizadeh M
Marra F
Bilia AR
Mowla SJ
Najafi F
Babaei E
author_sort Tahmasebi Mirgani M
collection DOAJ
description Maryam Tahmasebi Mirgani,1 Benedetta Isacchi,2 Majid Sadeghizadeh,1,* Fabio Marra,3 Anna Rita Bilia,2,* Seyed Javad Mowla,1 Farhood Najafi,4 Esmael Babaei51Department of Genetics, Tarbiat Modares University, Tehran, Iran; 2Department of Chemistry, University of Florence, Sesto Fiorentino, Italy; 3Department of Experimental and Clinical Medicine, University of Florence, Italy; 4Department of Resin and Additives, Institute for Color Science and Technology, Tehran, Iran; 5Department of Biology, University of Tabriz, Tabriz, Iran*These authors contributed equally to this workAbstract: 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.Keywords: glioblastoma, pluripotency gene, miRNA, dendrosomal curcumin
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spelling doaj.art-d11066e27a124419a4d3c844cf13c42e2022-12-21T23:08:31ZengDove Medical PressInternational Journal of Nanomedicine1178-20132014-01-012014Issue 140341715489Dendrosomal curcumin nanoformulation downregulates pluripotency genes via miR-145 activation in U87MG glioblastoma cellsTahmasebi Mirgani MIsacchi BSadeghizadeh MMarra FBilia ARMowla SJNajafi FBabaei EMaryam Tahmasebi Mirgani,1 Benedetta Isacchi,2 Majid Sadeghizadeh,1,* Fabio Marra,3 Anna Rita Bilia,2,* Seyed Javad Mowla,1 Farhood Najafi,4 Esmael Babaei51Department of Genetics, Tarbiat Modares University, Tehran, Iran; 2Department of Chemistry, University of Florence, Sesto Fiorentino, Italy; 3Department of Experimental and Clinical Medicine, University of Florence, Italy; 4Department of Resin and Additives, Institute for Color Science and Technology, Tehran, Iran; 5Department of Biology, University of Tabriz, Tabriz, Iran*These authors contributed equally to this workAbstract: 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.Keywords: glioblastoma, pluripotency gene, miRNA, dendrosomal curcuminhttp://www.dovepress.com/dendrosomal-curcumin-nanoformulation-downregulates-pluripotency-genes--a15489
spellingShingle Tahmasebi Mirgani M
Isacchi B
Sadeghizadeh M
Marra F
Bilia AR
Mowla SJ
Najafi F
Babaei E
Dendrosomal curcumin nanoformulation downregulates pluripotency genes via miR-145 activation in U87MG glioblastoma cells
International Journal of Nanomedicine
title Dendrosomal curcumin nanoformulation downregulates pluripotency genes via miR-145 activation in U87MG glioblastoma cells
title_full Dendrosomal curcumin nanoformulation downregulates pluripotency genes via miR-145 activation in U87MG glioblastoma cells
title_fullStr Dendrosomal curcumin nanoformulation downregulates pluripotency genes via miR-145 activation in U87MG glioblastoma cells
title_full_unstemmed Dendrosomal curcumin nanoformulation downregulates pluripotency genes via miR-145 activation in U87MG glioblastoma cells
title_short Dendrosomal curcumin nanoformulation downregulates pluripotency genes via miR-145 activation in U87MG glioblastoma cells
title_sort dendrosomal curcumin nanoformulation downregulates pluripotency genes via mir 145 activation in u87mg glioblastoma cells
url http://www.dovepress.com/dendrosomal-curcumin-nanoformulation-downregulates-pluripotency-genes--a15489
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