GD2 identifies cancer stemness in glioblastoma and phytoalexin library screen identifies potential novel natural inhibitors

Authors: NGUYEN, KHOA - Tulane University; MCCONNELL, EMILY - Tulane University; TRAN, MINH - Tulane University; BUROW, NATHAN - Tulane University; EDWARDS, ORIELLE - Tulane University; CHENG, THOMAS - Tulane University; CAVANAUGH, JANE - Duquesne University; FLAHERTY, PATRICK - Duquesne University; IZADPANAH, REZA - Tulane University; COLLINS-BUROW, BRIDGETTE - Tulane University; Boue, Stephen; BUROW, MATTHEW - Tulane University

Submitted to: International Journal of Molecular Sciences
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/11/2026
Publication Date: 4/14/2026
Citation: Nguyen, K., Mcconnell, E., Tran, M., Burow, N., Edwards, O., Cheng, T., Cavanaugh, J.E., Flaherty, P.T., Izadpanah, R., Collins-Burow, B.M., Boue, S.M., Burow, M.E. 2026. GD2 identifies cancer stemness in glioblastoma and phytoalexin library screen identifies potential novel natural inhibitors. International Journal of Molecular Sciences. https://doi.org/10.3390/ijms27083490.
DOI: https://doi.org/10.3390/ijms27083490

Interpretive Summary: Glioblastoma multiforme is one of the deadliest types of brain cancer in adults. It grows quickly, spreads easily in the brain, and is very hard to treat. Most patients only survive about a year after diagnosis. Because current treatments don’t work well, scientists are looking for new ways to fight this disease. This study focuses on a molecule called GD2, which is found in high levels in glioblastoma cells but not in healthy brain cells. GD2 might play a role in how the cancer spreads, but its exact function has been debated. Researchers used cancer cells with and without GD2 to see how it affects tumor behavior. They found that GD2 is linked to how the cancer moves and grows, especially in terms of its ability to change and survive under different conditions. The team also tested natural compounds from plants to see if any could stop the cancer from growing. Three of them, tuberosin, broussonin B, and glyceollin I, showed promise in stopping tumor growth in lab tests. Importantly, these natural compounds worked without changing GD2 levels, which suggests they fight the cancer in a different way. In short, this research strengthens the case for GD2’s role in glioblastoma and introduces new plant-based compounds that could lead to better treatments.

Technical Abstract: Glioblastoma multiforme (GBM) is the most aggressive and prevalent primary brain tumor in adults, characterized by rapid growth, diffuse infiltration, and a dismal prognosis. Despite advances in conventional therapies, median survival remains approximately one year, emphasizing the urgent need for novel therapeutic strategies. GD2, a disialoganglioside overexpressed in several malignancies, has been implicated in tumorigenesis and metastasis and has been identified as a cancer stem cell marker. While previous reports have identified high levels of GD2 expression in gliomas compared to normal brain tissue, its role in GBM stemness remains controversial. This study revisits prior findings refuting GD2’s involvement in GBM stemness by replicating key tumorigenesis experiments and further explores its impact on stemness properties such as migration and metabolic plasticity. Additionally, a phytochemical screen was used to identify natural compounds as potential inhibitors targeting GD2-mediated tumorigenesis. Our findings aim to clarify GD2’s role in GBM and provide insights into novel therapeutic interventions.