Modulating Wnt/Β-Catenin Signaling Pathway on U251 and T98g Glioblastoma Cell Lines Using a Combination of Paclitaxel and Temozolomide, a Molecular Docking Simulations and Gene Expression Study

Modulating Wnt/Β-Catenin Signaling Pathway on U251 and T98g Glioblastoma Cell Lines Using a Combination of Paclitaxel and Temozolomide, a Molecular Docking Simulations and Gene Expression Study Publisher

Jamalpour S¹ ; Alinezhad A² ; Sabah JT³ ; Vazifehmand R⁴ ; Behrooz AB⁵ ; Hamzah ASA⁶ ; Davazdahemami AA⁷ ; Homaie FM⁸ ; Maddah SM⁹

Show Affiliations

1. Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, 50603, Malaysia
2. Department of Clinical Pharmacy, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
3. Department of Pathological Analysis, Faculty of Science, Wasit University, Kut, Iraq
4. Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia (UPM), Serdang, Selangor Darul Ehsan, 43400, Malaysia
5. Nano Biotechnology Research Group, Department of Biochemistry, Faculty of Biotechnology and Bimolecular Sciences, University Putra Malaysia, Serdang, 43400, Malaysia
6. Nanobiotechnology Research Group, Department of Biochemistry, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor, 43400, Malaysia
7. Department of Biological Science and Technology, Isfahan Medical University, Isfahan, Iran
8. Department of Biochemistry, Science and Research University-Fars, Branch-Shiraz-Iran, Shiraz, Iran
9. Department of Biology, Yadegar-e-Imam Khomeini (RAH) Shahre Rey Branch, Islamic Azad University, Tehran, Iran

Source: Chemical and Pharmaceutical Bulletin Published:2023

Abstract

One of the most lethal cancers, glioblastoma (GBM), affects 14.5% of all central nervous system (CNS) tumors. Patients diagnosed with GBM have a meager median overall survival (OS) of 15 months. Extensive genetic analysis has shown that many dysregulated pathways, including the Wnt/β-catenin signaling system, contribute to the pathogenicity of GBM. Paclitaxel (PTX) and temozolomide (TMZ) are recognized to have therapeutic potential in several types of cancer, including GBM. This work aimed to examine the impact of PTX and TMZ on the human glioma cell lines U251 and T98G using molecular docking simulations and gene expression profiles in the Wnt/β-catenin signaling pathway. Standard procedure for Molecular Docking simulation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay, and Flow Cytometry assay was used. Genes implicated in the Wnt/β-catenin signaling pathway, including Dvl, Axin, APC, β-catenin, and glycogen synthase kinase3-β (GSK3β), were subjected to real-time PCR. The estimated parameters for targets revealed that the average binding energy and inhibition constant (Ki) for the DVL, β-Catenin, and GSK3β, when targeted by PTX, were - 5.01 kcal/mol, - 5.4 kcal/mol, and - 9.06 kcal/mol, respectively. This energy range was - 6.34 kcal/mol for DVL, - 5.52 kcal/mol for β-Catenin, and - 5.66 kcal/mol for GSK3β as a result of TMZ's inhibitory actions. Gene expression analyses indicated that PTX and PTX/TMZ suppressed GSK3β (p<0.05). GSK3β from the Wnt/β-catenin signaling pathway was significantly targeted by PTX alone, and adding TMZ to PTX may improve the efficacy of glioblastoma treatment. In addition, the GSK3β gene may help GBM therapy strategies as a potential PTX target. © 2023 The Pharmaceutical Society of Japan.

Related Docs

View other Related Docs

1. Temozolomide and Tranilast Synergistic Antiproliferative Effect on Human Glioblastoma Multiforme Cell Line (U87mg), Medical Journal of the Islamic Republic of Iran (2019)

2. The Importance of the Circrna/Wnt Axis in Gliomas: Biological Functions and Clinical Opportunities, Pathology Research and Practice (2024)

3. Resveratrol As an Antitumor Agent for Glioblastoma Multiforme: Targeting Resistance and Promoting Apoptotic Cell Deaths, Acta Histochemica (2023)

4. A Comprehensive Insight Into the Correlation Between Ncrnas and the Wnt/Β-Catenin Signalling Pathway in Gastric Cancer Pathogenesis, Cell Communication and Signaling (2023)

5. Investigation the Effect of Adenosine A1 Receptor Agonist and Antagonist on P53 Gene Expression, and Apoptosis Pathways and Rate in U87mg Multiform Glioblastoma, Journal of Isfahan Medical School (2021)

6. Evaluation of Traf3ip2 Gene Expression in Brain Tumor Tissue of Patients With Glioblastoma Multiforme in Comparison to Non-Tumoral Brain Tissue, Middle East Journal of Cancer (2023)

7. A Glance at Glioblastoma Molecular Culprits Through In-Silico Analysis, Gene Reports (2021)

8. Evaluation of Antitumor Effects of Aspirin and Lgk974 Drugs on Cellular Signaling Pathways, Cell Cycle and Apoptosis in Colorectal Cancer Cell Lines Compared to Oxaliplatin Drug, Fundamental and Clinical Pharmacology (2020)

Experts (# of related papers)

View all Related Experts

Parvin Mahzouni (2)

Zeinolabedin Sharifiandastjedy (1)

Style	Citing Format
MLA	Jamalpour S, et al.. "Modulating Wnt/Β-Catenin Signaling Pathway on U251 and T98g Glioblastoma Cell Lines Using a Combination of Paclitaxel and Temozolomide, a Molecular Docking Simulations and Gene Expression Study." Chemical and Pharmaceutical Bulletin, vol. 71, no. 10, 2023, pp. 766-774.
APA	Jamalpour S, Alinezhad A, Sabah JT, Vazifehmand R, Behrooz AB, Hamzah ASA, Davazdahemami AA, Homaie FM, Maddah SM (2023). Modulating Wnt/Β-Catenin Signaling Pathway on U251 and T98g Glioblastoma Cell Lines Using a Combination of Paclitaxel and Temozolomide, a Molecular Docking Simulations and Gene Expression Study. Chemical and Pharmaceutical Bulletin, 71(10), 766-774.
Chicago	Jamalpour S, Alinezhad A, Sabah JT, Vazifehmand R, Behrooz AB, Hamzah ASA, Davazdahemami AA, Homaie FM, Maddah SM. "Modulating Wnt/Β-Catenin Signaling Pathway on U251 and T98g Glioblastoma Cell Lines Using a Combination of Paclitaxel and Temozolomide, a Molecular Docking Simulations and Gene Expression Study." Chemical and Pharmaceutical Bulletin 71, no. 10 (2023): 766-774.
Harvard	Jamalpour S et al. (2023) 'Modulating Wnt/Β-Catenin Signaling Pathway on U251 and T98g Glioblastoma Cell Lines Using a Combination of Paclitaxel and Temozolomide, a Molecular Docking Simulations and Gene Expression Study', Chemical and Pharmaceutical Bulletin, 71(10), pp. 766-774.
Vancouver	Jamalpour S, Alinezhad A, Sabah JT, Vazifehmand R, Behrooz AB, Hamzah ASA, et al.. Modulating Wnt/Β-Catenin Signaling Pathway on U251 and T98g Glioblastoma Cell Lines Using a Combination of Paclitaxel and Temozolomide, a Molecular Docking Simulations and Gene Expression Study. Chemical and Pharmaceutical Bulletin. 2023;71(10):766-774.
BibTex	@article{ author = {Jamalpour S and Alinezhad A and Sabah JT and Vazifehmand R and Behrooz AB and Hamzah ASA and Davazdahemami AA and Homaie FM and Maddah SM}, title = {Modulating Wnt/Β-Catenin Signaling Pathway on U251 and T98g Glioblastoma Cell Lines Using a Combination of Paclitaxel and Temozolomide, a Molecular Docking Simulations and Gene Expression Study}, journal = {Chemical and Pharmaceutical Bulletin}, volume = {71}, number = {10}, pages = {766-774}, year = {2023} }
RIS	TY - JOUR AU - Jamalpour S AU - Alinezhad A AU - Sabah JT AU - Vazifehmand R AU - Behrooz AB AU - Hamzah ASA AU - Davazdahemami AA AU - Homaie FM AU - Maddah SM TI - Modulating Wnt/Β-Catenin Signaling Pathway on U251 and T98g Glioblastoma Cell Lines Using a Combination of Paclitaxel and Temozolomide, a Molecular Docking Simulations and Gene Expression Study JO - Chemical and Pharmaceutical Bulletin VL - 71 IS - 10 SP - 766 EP - 774 PY - 2023 ER -

Science Communicator Platform

Authors

Authors Affiliations

Abstract