Deciphering the dose-dependent effects of thymoquinone on cellular proliferation and transcriptomic changes in A172 glioblastoma cells.
Glioblastoma multiforme (GBM), the most prevalent primary malignant brain tumor in adults, exhibits a dismal 6.9% five-year survival rate post-diagnosis. Thymoquinone (TQ), the most abundant bioactive compound in Nigella sativa, has been extensively researched for its anticancer properties across va...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0318185 |
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| author | Rachana Pandey Purushothaman Natarajan Umesh K Reddy Wei Du Cristian Sirbu Moussa Sissoko Gerald R Hankins |
| author_facet | Rachana Pandey Purushothaman Natarajan Umesh K Reddy Wei Du Cristian Sirbu Moussa Sissoko Gerald R Hankins |
| author_sort | Rachana Pandey |
| collection | DOAJ |
| description | Glioblastoma multiforme (GBM), the most prevalent primary malignant brain tumor in adults, exhibits a dismal 6.9% five-year survival rate post-diagnosis. Thymoquinone (TQ), the most abundant bioactive compound in Nigella sativa, has been extensively researched for its anticancer properties across various human cancers. However, its specific anti-cancer mechanisms and pathways in glioblastoma remain to be completely elucidated. In this study, we assessed the impact of different TQ concentrations on the viability of A172 cells using WST-8 and Toluidine blue assays, followed by RNA sequencing (RNA-Seq) to identify differentially expressed genes (DEGs). We confirmed their expression levels through quantitative RT-PCR and performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for these DEGs. RNA-seq revealed no significant gene expression changes at 2.5 μM and 5 μM TQ concentrations. However, at 25 μM and 50 μM, TQ significantly reduced cell viability dose-dependently. We identified 1548 DEGs at 25 μM TQ (684 up-regulated, 864 down-regulated) and 2797 DEGs at 50 μM TQ (1528 up-regulated, 1269 downregulated), with 1202 DEGs common to both concentrations. TQ inhibited key pathways such as PI3K-Akt signaling, calcium signaling, focal adhesion, and ECM-receptor interaction in A172 cells. It downregulated several potential oncogenes (e.g., AEBP1, MIAT) and genes linked to GBM proliferation and migration (e.g., SOCS2, HCP5) while modulating Wnt signaling and up-regulating tumor suppressor genes (e.g., SPRY4, BEX2). TQ also affected p53 downstream targets, maintaining p53 levels. This study elucidates the anti-cancer mechanisms of TQ in A172 GBM cells, underscoring its effects on multiple signaling pathways and positioning TQ as a promising candidate for innovative glioblastoma treatment strategies. |
| format | Article |
| id | doaj-art-0390999e8575485b90d1c19c7887f698 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-0390999e8575485b90d1c19c7887f6982025-02-05T05:31:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01201e031818510.1371/journal.pone.0318185Deciphering the dose-dependent effects of thymoquinone on cellular proliferation and transcriptomic changes in A172 glioblastoma cells.Rachana PandeyPurushothaman NatarajanUmesh K ReddyWei DuCristian SirbuMoussa SissokoGerald R HankinsGlioblastoma multiforme (GBM), the most prevalent primary malignant brain tumor in adults, exhibits a dismal 6.9% five-year survival rate post-diagnosis. Thymoquinone (TQ), the most abundant bioactive compound in Nigella sativa, has been extensively researched for its anticancer properties across various human cancers. However, its specific anti-cancer mechanisms and pathways in glioblastoma remain to be completely elucidated. In this study, we assessed the impact of different TQ concentrations on the viability of A172 cells using WST-8 and Toluidine blue assays, followed by RNA sequencing (RNA-Seq) to identify differentially expressed genes (DEGs). We confirmed their expression levels through quantitative RT-PCR and performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for these DEGs. RNA-seq revealed no significant gene expression changes at 2.5 μM and 5 μM TQ concentrations. However, at 25 μM and 50 μM, TQ significantly reduced cell viability dose-dependently. We identified 1548 DEGs at 25 μM TQ (684 up-regulated, 864 down-regulated) and 2797 DEGs at 50 μM TQ (1528 up-regulated, 1269 downregulated), with 1202 DEGs common to both concentrations. TQ inhibited key pathways such as PI3K-Akt signaling, calcium signaling, focal adhesion, and ECM-receptor interaction in A172 cells. It downregulated several potential oncogenes (e.g., AEBP1, MIAT) and genes linked to GBM proliferation and migration (e.g., SOCS2, HCP5) while modulating Wnt signaling and up-regulating tumor suppressor genes (e.g., SPRY4, BEX2). TQ also affected p53 downstream targets, maintaining p53 levels. This study elucidates the anti-cancer mechanisms of TQ in A172 GBM cells, underscoring its effects on multiple signaling pathways and positioning TQ as a promising candidate for innovative glioblastoma treatment strategies.https://doi.org/10.1371/journal.pone.0318185 |
| spellingShingle | Rachana Pandey Purushothaman Natarajan Umesh K Reddy Wei Du Cristian Sirbu Moussa Sissoko Gerald R Hankins Deciphering the dose-dependent effects of thymoquinone on cellular proliferation and transcriptomic changes in A172 glioblastoma cells. PLoS ONE |
| title | Deciphering the dose-dependent effects of thymoquinone on cellular proliferation and transcriptomic changes in A172 glioblastoma cells. |
| title_full | Deciphering the dose-dependent effects of thymoquinone on cellular proliferation and transcriptomic changes in A172 glioblastoma cells. |
| title_fullStr | Deciphering the dose-dependent effects of thymoquinone on cellular proliferation and transcriptomic changes in A172 glioblastoma cells. |
| title_full_unstemmed | Deciphering the dose-dependent effects of thymoquinone on cellular proliferation and transcriptomic changes in A172 glioblastoma cells. |
| title_short | Deciphering the dose-dependent effects of thymoquinone on cellular proliferation and transcriptomic changes in A172 glioblastoma cells. |
| title_sort | deciphering the dose dependent effects of thymoquinone on cellular proliferation and transcriptomic changes in a172 glioblastoma cells |
| url | https://doi.org/10.1371/journal.pone.0318185 |
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