Repurposing Nelfinavir: AIM2 Inflammasome-Driven Anti-tumor Effects in Glioblastoma
Meena, D.; Chhipa, S.; Solanki, P.; Sha, L.; Jha, S.
Show abstract
Nelfinavir (NFR), originally developed as an antiretroviral agent for the human immunodeficiency virus, has demonstrated anti-cancer properties across various malignancies; however, its therapeutic potential in Glioblastoma (GBM) remains largely unexplored. In the present study, we investigated the anti-tumor effects of NFR in GBM using a comprehensive panel of experimental models, including established GBM cell lines, GBM cell line-derived spheroids, patient-derived primary glioma cells, and patient-derived glioma organoids. We further evaluated the synergistic potential of NFR in combination with standard chemotherapeutic agents, Carboplatin and Doxorubicin, across these platforms. In vitro analyses revealed that NFR significantly inhibits GBM cell proliferation and induces both apoptotic and necrotic cell death. Mechanistically, we identified activation of the AIM2 inflammasome as a potential additional pathway mediating the anti-tumor effects of NFR. Collectively, our findings highlight NFR as a promising therapeutic candidate for GBM, exerting its effects through anti-proliferative and pro-death mechanisms potentially linked to AIM2 inflammasome activation.
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