Version 1
: Received: 25 January 2024 / Approved: 26 January 2024 / Online: 26 January 2024 (08:41:19 CET)
How to cite:
Pandey, R.; Natarajan, P.; Reddy, U.K.; Du, W.; Sirbu, C.; Sissoko, M.; Hankins, G.R. Deciphering the Dose-Dependent Effects of Thymoquinone on Transcriptomic Changes and Cellular Proliferation in Glioblastoma. Preprints2024, 2024011894. https://doi.org/10.20944/preprints202401.1894.v1
Pandey, R.; Natarajan, P.; Reddy, U.K.; Du, W.; Sirbu, C.; Sissoko, M.; Hankins, G.R. Deciphering the Dose-Dependent Effects of Thymoquinone on Transcriptomic Changes and Cellular Proliferation in Glioblastoma. Preprints 2024, 2024011894. https://doi.org/10.20944/preprints202401.1894.v1
Pandey, R.; Natarajan, P.; Reddy, U.K.; Du, W.; Sirbu, C.; Sissoko, M.; Hankins, G.R. Deciphering the Dose-Dependent Effects of Thymoquinone on Transcriptomic Changes and Cellular Proliferation in Glioblastoma. Preprints2024, 2024011894. https://doi.org/10.20944/preprints202401.1894.v1
APA Style
Pandey, R., Natarajan, P., Reddy, U.K., Du, W., Sirbu, C., Sissoko, M., & Hankins, G.R. (2024). Deciphering the Dose-Dependent Effects of Thymoquinone on Transcriptomic Changes and Cellular Proliferation in Glioblastoma. Preprints. https://doi.org/10.20944/preprints202401.1894.v1
Chicago/Turabian Style
Pandey, R., Moussa Sissoko and Gerald R Hankins. 2024 "Deciphering the Dose-Dependent Effects of Thymoquinone on Transcriptomic Changes and Cellular Proliferation in Glioblastoma" Preprints. https://doi.org/10.20944/preprints202401.1894.v1
Abstract
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 anti-cancer properties across various human cancers. Yet, its specific anticancer mechanisms and pathways in glioblastoma remain to be 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 in a dose-dependent manner. We identified 1548 DEGs at 25 µM TQ (684 upregulated, 864 downregulated) and 2797 DEGs at 50 µM TQ (1528 upregulated, 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 upregulating tumor suppressor genes (e.g., SPRY4, BEX2). TQ also affected p53 downstream targets, maintaining p53 levels. This study elucidates the anticancer 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.
Biology and Life Sciences, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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