ΑCT1 peptide sensitizes glioma cells to temozolomide in a glioblastoma organoid platform. Issue 4 (3rd January 2023)

• Record Type: Journal Article
• Authors: Che, Jingru; DePalma, Thomas J.; Sivakumar, Hemamylammal; Mezache, Louisa S.; Tallman, Miranda M.; Venere, Monica; Swindle‐Reilly, Katelyn; Veeraraghavan, Rengasayee; Skardal, Aleksander
• Is Part Of: Biotechnology and bioengineering. Volume 120:Issue 4(2023)
• Page Start: 1108
• Page End: 1119
• Publication Date: 2023-01-03
• Subjects: Connexin 43 -- glioblastoma -- organoids -- temozolomide; Biotechnology -- Periodicals; Bioengineering -- Periodicals; 660.6
• DOI: 10.1002/bit.28313
• Languages: English
• ISSNs: 0006-3592

Abstract

Abstract: Glioblastoma (GBM) is the most common form of brain cancer. Even with aggressive treatment, tumor recurrence is almost universal and patient prognosis is poor because many GBM cell subpopulations, especially the mesenchymal and glioma stem cell populations, are resistant to temozolomide (TMZ), the most commonly used chemotherapeutic in GBM. For this reason, there is an urgent need for the development of new therapies that can more effectively treat GBM. Several recent studies have indicated that high expression of connexin 43 (Cx43) in GBM is associated with poor patient outcomes. It has been hypothesized that inhibition of the Cx43 hemichannels could prevent TMZ efflux and sensitize otherwise resistance cells to the treatment. In this study, we use a three‐dimensional organoid model of GBM to demonstrate that combinatorial treatment with TMZ and αCT1, a Cx43 mimetic peptide, significantly improves treatment efficacy in certain populations of GBM. Confocal imaging was used to visualize changes in Cx43 expression in response to combinatorial treatment. These results indicate that Cx43 inhibition should be pursued further as an improved treatment for GBM. Abstract : In this study, the authors test a combinatorial treatment for glioblastoma using a 3D hydrogel tumor organoid. Combining the standard chemotherapeutic temozolomide (TMZ) with a connexin 43 (Cx43) mimetic peptide, αCT1, leads to increased tumor cell death and changes in protein expression. The results indicate that Cx43 could be an intriguing target for novel therapies.