Abstract 7156: Inhibition in the proliferation of pediatric glioblastoma facilitated with atypical protein kinase c inhibitors

Abstract Pediatric glioblastoma (pGBM) is an aggressive brain tumor with a five-year survival rate of approximately 5%. Current therapeutic options are limited, primarily due to poor blood-brain barrier penetration of available drugs. Atypical Protein Kinase C (aPKC) isoforms, Protein Kinase C- iota (PKC-ι) and Protein Kinase C- zeta (PKC-ζ), play crucial roles in tumor cell proliferation and survival. In this study, we investigated the effects of ICA-1S 5-amino-1-((1R,2S,3S,4R)-2,3-dihydroxy-4-methylcyclopentyl)-1H-imidazole-4-carboxamide, a selective PKC-ι inhibitor, and ζ-Stat 8-hydroxy-1,3,6-naphthalenetrisulfonic acid, a PKC-ζ inhibitor, on pediatric glioblastoma SF188 cells. SF188 cells (50,000/well) were seeded in 6-well plates and treated with varying concentrations of ICA-1S and ζ-Stat for three days. On the fourth day, cell viability was determined to generate a dose-response curve. ICA-1S showed maximal inhibition at 75 μM, while ζ-Stat decreased proliferation by approximately 50% at 20 μM. These results suggest that both PKC-ι and PKC-ζ contribute to SF188 cell proliferation. To explore the molecular mechanisms underlying this inhibition, protein lysates from treated and untreated cells were analyzed via Sodium Dodecyl Sulfate-Polyacrylamide Gel Electrophoresis (SDS-PAGE) and Western blotting. Both ICA-1S and ζ-Stat treatments resulted in downregulation of PKC-ι and PKC-ζ protein expression compared to control samples. Furthermore, expression of the apoptotic marker Caspase-3 was found to be decreased in drug-treated cells, suggesting activation of apoptotic signaling following inhibition of aPKCs. These findings indicate that selective inhibition of aPKCs suppresses proliferation and induces apoptosis in pediatric glioblastoma cells. Ongoing and future studies will employ immunoprecipitation, immunofluorescence, and WST assays to elucidate downstream signaling pathways and validate ICA-1S and ζ-Stat as potential therapeutic candidates for pediatric glioblastoma. Citation Format: Shreejana Rimal, Grazielly Teodoro, Gaurab Raj Khanal, Mildred Acevedo-Duncan. Inhibition in the proliferation of pediatric glioblastoma facilitated with atypical protein kinase c inhibitors abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7156.