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Novel Derivatives of Tetrahydrobenzo (g) Imidazo[α-1,2] Quinoline Induce Apoptosis Via ROS Production in the Glioblastoma Multiforme Cells, U-87MG

BACKGROUND: Despite newer therapeutic approaches against glioblastoma multiforme (GBM), the severely poor prognosis and treatment resistance are still disadvantages that slow down the patient’s recovery process. Consistent with the need to develop more effective and optimized therapies to control GB...

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Autores principales: Mostafavi Hosseini, Fatemeh, Ashourpour, Maryam, Taheri, Salman, Tavakoli-Yaraki, Masoumeh, Salami, Siamak, Shahsavari, Zahra, Kazerouni, Faranak
Formato: Online Artículo Texto
Lenguaje:English
Publicado: West Asia Organization for Cancer Prevention 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9930943/
https://www.ncbi.nlm.nih.gov/pubmed/36444602
http://dx.doi.org/10.31557/APJCP.2022.23.11.3885
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author Mostafavi Hosseini, Fatemeh
Ashourpour, Maryam
Taheri, Salman
Tavakoli-Yaraki, Masoumeh
Salami, Siamak
Shahsavari, Zahra
Kazerouni, Faranak
author_facet Mostafavi Hosseini, Fatemeh
Ashourpour, Maryam
Taheri, Salman
Tavakoli-Yaraki, Masoumeh
Salami, Siamak
Shahsavari, Zahra
Kazerouni, Faranak
author_sort Mostafavi Hosseini, Fatemeh
collection PubMed
description BACKGROUND: Despite newer therapeutic approaches against glioblastoma multiforme (GBM), the severely poor prognosis and treatment resistance are still disadvantages that slow down the patient’s recovery process. Consistent with the need to develop more effective and optimized therapies to control GBM cell growth, the effects of a new series of tetrahydrobenzo(g)imidazo[α-1,2]quinolone derivatives on GBM cell growth and the underlying mechanism is investigated in the current study. METHODS: U-87MG cell line, glioblastoma multiforme and normal skin fibroblast cell line, AGO1522 were used to study the anticancer effects of 5 derivatives of tetrahydrobenzo(g)imidazo[α-1,2]quinolone and paclitaxel as a standard drug. The cytotoxic effect on cell growth was assessed using the MTT assay. Annexin V FITC staining and PI staining were applied to detect apoptosis and cell cycle distribution using flow cytometry. The extent of reactive oxygen species (ROS) formation was assessed using the fluorescent probe 7-dichlorofluorescin diacetate and caspase-3 activity using the colorimetric assay kit. RESULTS: Among the 5 derivatives of tetrahydrobenzo(g)imidazo[α-1,2]quinolone, the 5c derivative (5-(6-bromo-2-chloroquinolin-3-yl)-9a-hydroxy-8,8-dimethyl-4-Nitro-2,3,5,5a,7,8,9,9a-octahydroimidazo[α-1,2]quinoline-6(1H)) showed the strongest cytotoxic effect on U-87MG cells in a time and Dose-dependent manner compared to the other derivatives and paclitaxel. The IC(50) (11.91 M) of the 5c derivative induced apoptosis accompanied by a significant increase in sub-G1 and super-G2 phases of U-87MG cells. The increased level of cellular ROS and caspase 3 activity after treatment of U-87MG cells with 5c derivative was significant compared to untreated cells. CONCLUSION: Our data provide insights into the potent anticancer effects of the 5c-derivative of tetrahydrobenzo(g)imidazo[α-1,2]quinolone on GBM cells via the caspase-dependent apoptotic pathway, which may merit further attention.
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spelling pubmed-99309432023-02-16 Novel Derivatives of Tetrahydrobenzo (g) Imidazo[α-1,2] Quinoline Induce Apoptosis Via ROS Production in the Glioblastoma Multiforme Cells, U-87MG Mostafavi Hosseini, Fatemeh Ashourpour, Maryam Taheri, Salman Tavakoli-Yaraki, Masoumeh Salami, Siamak Shahsavari, Zahra Kazerouni, Faranak Asian Pac J Cancer Prev Research Article BACKGROUND: Despite newer therapeutic approaches against glioblastoma multiforme (GBM), the severely poor prognosis and treatment resistance are still disadvantages that slow down the patient’s recovery process. Consistent with the need to develop more effective and optimized therapies to control GBM cell growth, the effects of a new series of tetrahydrobenzo(g)imidazo[α-1,2]quinolone derivatives on GBM cell growth and the underlying mechanism is investigated in the current study. METHODS: U-87MG cell line, glioblastoma multiforme and normal skin fibroblast cell line, AGO1522 were used to study the anticancer effects of 5 derivatives of tetrahydrobenzo(g)imidazo[α-1,2]quinolone and paclitaxel as a standard drug. The cytotoxic effect on cell growth was assessed using the MTT assay. Annexin V FITC staining and PI staining were applied to detect apoptosis and cell cycle distribution using flow cytometry. The extent of reactive oxygen species (ROS) formation was assessed using the fluorescent probe 7-dichlorofluorescin diacetate and caspase-3 activity using the colorimetric assay kit. RESULTS: Among the 5 derivatives of tetrahydrobenzo(g)imidazo[α-1,2]quinolone, the 5c derivative (5-(6-bromo-2-chloroquinolin-3-yl)-9a-hydroxy-8,8-dimethyl-4-Nitro-2,3,5,5a,7,8,9,9a-octahydroimidazo[α-1,2]quinoline-6(1H)) showed the strongest cytotoxic effect on U-87MG cells in a time and Dose-dependent manner compared to the other derivatives and paclitaxel. The IC(50) (11.91 M) of the 5c derivative induced apoptosis accompanied by a significant increase in sub-G1 and super-G2 phases of U-87MG cells. The increased level of cellular ROS and caspase 3 activity after treatment of U-87MG cells with 5c derivative was significant compared to untreated cells. CONCLUSION: Our data provide insights into the potent anticancer effects of the 5c-derivative of tetrahydrobenzo(g)imidazo[α-1,2]quinolone on GBM cells via the caspase-dependent apoptotic pathway, which may merit further attention. West Asia Organization for Cancer Prevention 2022-11 /pmc/articles/PMC9930943/ /pubmed/36444602 http://dx.doi.org/10.31557/APJCP.2022.23.11.3885 Text en https://creativecommons.org/licenses/by-nc/4.0/This work is licensed under a Creative Commons Attribution-Non Commercial 4.0 International License. https://creativecommons.org/licenses/by-nc/4.0/
spellingShingle Research Article
Mostafavi Hosseini, Fatemeh
Ashourpour, Maryam
Taheri, Salman
Tavakoli-Yaraki, Masoumeh
Salami, Siamak
Shahsavari, Zahra
Kazerouni, Faranak
Novel Derivatives of Tetrahydrobenzo (g) Imidazo[α-1,2] Quinoline Induce Apoptosis Via ROS Production in the Glioblastoma Multiforme Cells, U-87MG
title Novel Derivatives of Tetrahydrobenzo (g) Imidazo[α-1,2] Quinoline Induce Apoptosis Via ROS Production in the Glioblastoma Multiforme Cells, U-87MG
title_full Novel Derivatives of Tetrahydrobenzo (g) Imidazo[α-1,2] Quinoline Induce Apoptosis Via ROS Production in the Glioblastoma Multiforme Cells, U-87MG
title_fullStr Novel Derivatives of Tetrahydrobenzo (g) Imidazo[α-1,2] Quinoline Induce Apoptosis Via ROS Production in the Glioblastoma Multiforme Cells, U-87MG
title_full_unstemmed Novel Derivatives of Tetrahydrobenzo (g) Imidazo[α-1,2] Quinoline Induce Apoptosis Via ROS Production in the Glioblastoma Multiforme Cells, U-87MG
title_short Novel Derivatives of Tetrahydrobenzo (g) Imidazo[α-1,2] Quinoline Induce Apoptosis Via ROS Production in the Glioblastoma Multiforme Cells, U-87MG
title_sort novel derivatives of tetrahydrobenzo (g) imidazo[α-1,2] quinoline induce apoptosis via ros production in the glioblastoma multiforme cells, u-87mg
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9930943/
https://www.ncbi.nlm.nih.gov/pubmed/36444602
http://dx.doi.org/10.31557/APJCP.2022.23.11.3885
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