Combination Therapy with Nanomicellar-Curcumin and Temozolomide for In Vitro Therapy of Glioblastoma Multiforme via Wnt
- PDF / 3,059,154 Bytes
- 13 Pages / 595.276 x 790.866 pts Page_size
- 32 Downloads / 183 Views
Combination Therapy with Nanomicellar-Curcumin and Temozolomide for In Vitro Therapy of Glioblastoma Multiforme via Wnt Signaling Pathways Ali Bagherian 1 & Rajab Mardani 2 & Bostan Roudi 1 & Mohsen Taghizadeh 3 & Hamid Reza Banfshe 4 & Amir Ghaderi 5 & Amirhossein Davoodvandi 6 & Samane Shamollaghamsari 6 & Michael R. Hamblin 7,8 & Hamed Mirzaei 3 Received: 4 April 2020 / Accepted: 16 June 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Glioblastoma (GBM) is the most serious brain tumor and shows a high rate of drug resistance. Wnt signaling is a very important pathway in GBM that can activate/inhibit other pathways, such as apoptosis and autophagy. In this study, we evaluated the efficacy of a combination of temozolomide (TMZ) plus curcumin or nanomicellar-curcumin on the inhibition of GBM growth in vitro, via effects on autophagy, apoptosis, and the Wnt signaling pathway. Two concentrations of curcumin and nanomicellarcurcumin (i.e., 20 μM and 50 μM) alone, and in combination with TMZ (50 μM) were used to induce cytotoxicity in the U87 GBM cell line. Wnt signaling–, autophagy-, and apoptosis-related genes were assessed by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and Western blots. All treatments (except 20 μM curcumin alone) significantly decreased the viability of U87 cells compared to controls. Curcumin (50 μM), nanomicellar-curcumin alone and in combination with TMZ significantly decreased the invasion and migration of U87 cells. Autophagy-related proteins (Beclin 1, LC3-I, LC3-II) were significantly increased. Apoptosis-related proteins (Bcl-2 and caspase 8) were also significantly increased, while Bax protein was significantly decreased. The expression levels of Wnt pathway–associated genes (β-catenin, cyclin D1, Twist, and ZEB1) were significantly reduced. Keywords Curcumin . Glioblastoma . Nanomicelles . Temozolomide . Wnt signaling . Autophagy . Apoptosis
Introduction * Hamed Mirzaei [email protected]; [email protected] 1
Department of Biology, Faculty of Science, Islamic Azad University, Damghan Branch, Damghan, Iran
2
Department of Biochemistry, Pasteur Institute of Iran, Tehran, Iran
3
Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
4
Department of Pharmacology, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
5
Department of Addiction Studies, School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
6
Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
7
Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, 40 Blossom Street, Boston, MA 02114, USA
8
Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, Johannesburg 2028, South Africa
Despite significant developments in therapy during the past decades, glioblastoma (GBM) remains a life-threatening brain tumor, with a med
Data Loading...
