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Elucidating the Anti-Tumorigenic Efficacy of Oltipraz, a Dithiolethione, in Glioblastoma
Glioblastoma multiforme (GBM), the most aggressive primary brain tumor, displays a highly infiltrative growth pattern and remains refractory to chemotherapy. Phytochemicals carrying specificity and low cytotoxicity may serve as potent and safer alternatives to conventional chemotherapy for treating...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9562012/ https://www.ncbi.nlm.nih.gov/pubmed/36231019 http://dx.doi.org/10.3390/cells11193057 |
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author | Kapoor-Narula, Upasana Lenka, Nibedita |
author_facet | Kapoor-Narula, Upasana Lenka, Nibedita |
author_sort | Kapoor-Narula, Upasana |
collection | PubMed |
description | Glioblastoma multiforme (GBM), the most aggressive primary brain tumor, displays a highly infiltrative growth pattern and remains refractory to chemotherapy. Phytochemicals carrying specificity and low cytotoxicity may serve as potent and safer alternatives to conventional chemotherapy for treating GBM. We have evaluated the anticancer effects of Oltipraz (Olt), a synthetic dithiolethione found in many vegetables, including crucifers. While Olt exposure was non-toxic to the HEK-293 cell line, it impaired the cell growth in three GBM cell lines (LN18, LN229, and U-87 MG), arresting those at the G2/M phase. Olt-exposed GBM cells induced the generation of reactive oxygen species (ROS), mitochondrial depolarization, caspase 3/7-mediated apoptosis, nuclear condensation, and DNA fragmentation, and decreased glutathione, a natural ROS scavenger, as well as vimentin and β-catenin, the EMT-associated markers. Its effect on a subpopulation of GBM cells exhibiting glioblastoma stem cell (GSCs)-like characteristics revealed a reduced expression of Oct4, Sox2, CD133, CD44, and a decrease in ALDH(+), Nestin(+) and CD44(+) cells. In contrast, there was an increase in the expression of GFAP and GFAP(+) cells. The Olt also significantly suppressed the oncosphere-forming ability of cells. Its efficacy was further validated in vivo, wherein oral administration of Olt could suppress the ectopically established GBM tumor growth in SCID mice. However, there was no alteration in body weight, organ ratio, and biochemical parameters, reflecting the absence of any toxicity otherwise. Together, our findings could demonstrate the promising chemotherapeutic efficacy of Olt with potential implications in treating GBM. |
format | Online Article Text |
id | pubmed-9562012 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-95620122022-10-15 Elucidating the Anti-Tumorigenic Efficacy of Oltipraz, a Dithiolethione, in Glioblastoma Kapoor-Narula, Upasana Lenka, Nibedita Cells Article Glioblastoma multiforme (GBM), the most aggressive primary brain tumor, displays a highly infiltrative growth pattern and remains refractory to chemotherapy. Phytochemicals carrying specificity and low cytotoxicity may serve as potent and safer alternatives to conventional chemotherapy for treating GBM. We have evaluated the anticancer effects of Oltipraz (Olt), a synthetic dithiolethione found in many vegetables, including crucifers. While Olt exposure was non-toxic to the HEK-293 cell line, it impaired the cell growth in three GBM cell lines (LN18, LN229, and U-87 MG), arresting those at the G2/M phase. Olt-exposed GBM cells induced the generation of reactive oxygen species (ROS), mitochondrial depolarization, caspase 3/7-mediated apoptosis, nuclear condensation, and DNA fragmentation, and decreased glutathione, a natural ROS scavenger, as well as vimentin and β-catenin, the EMT-associated markers. Its effect on a subpopulation of GBM cells exhibiting glioblastoma stem cell (GSCs)-like characteristics revealed a reduced expression of Oct4, Sox2, CD133, CD44, and a decrease in ALDH(+), Nestin(+) and CD44(+) cells. In contrast, there was an increase in the expression of GFAP and GFAP(+) cells. The Olt also significantly suppressed the oncosphere-forming ability of cells. Its efficacy was further validated in vivo, wherein oral administration of Olt could suppress the ectopically established GBM tumor growth in SCID mice. However, there was no alteration in body weight, organ ratio, and biochemical parameters, reflecting the absence of any toxicity otherwise. Together, our findings could demonstrate the promising chemotherapeutic efficacy of Olt with potential implications in treating GBM. MDPI 2022-09-29 /pmc/articles/PMC9562012/ /pubmed/36231019 http://dx.doi.org/10.3390/cells11193057 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kapoor-Narula, Upasana Lenka, Nibedita Elucidating the Anti-Tumorigenic Efficacy of Oltipraz, a Dithiolethione, in Glioblastoma |
title | Elucidating the Anti-Tumorigenic Efficacy of Oltipraz, a Dithiolethione, in Glioblastoma |
title_full | Elucidating the Anti-Tumorigenic Efficacy of Oltipraz, a Dithiolethione, in Glioblastoma |
title_fullStr | Elucidating the Anti-Tumorigenic Efficacy of Oltipraz, a Dithiolethione, in Glioblastoma |
title_full_unstemmed | Elucidating the Anti-Tumorigenic Efficacy of Oltipraz, a Dithiolethione, in Glioblastoma |
title_short | Elucidating the Anti-Tumorigenic Efficacy of Oltipraz, a Dithiolethione, in Glioblastoma |
title_sort | elucidating the anti-tumorigenic efficacy of oltipraz, a dithiolethione, in glioblastoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9562012/ https://www.ncbi.nlm.nih.gov/pubmed/36231019 http://dx.doi.org/10.3390/cells11193057 |
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