Isoliensinine Orchestrates PLCγ1-Driven Apoptosis by Regulating Ca²⁺ and PKC Signaling in Glioblastoma.

Authors

Yu-Teng Chang, Yueh-Tsung Lee

Published in

Free radical biology & medicine. Oct 14, 2026. Epub Oct 14, 2026.

Abstract

Glioblastoma remains one of the most aggressive primary brain tumors, and the identification of pharmacologically targetable signaling vulnerabilities is essential for developing new therapeutic strategies. This study tested the hypothesis that isoliensinine suppresses glioblastoma cell survival by disrupting phospholipase C gamma 1 (PLCG1)-dependent calcium and diacylglycerol signaling. Human glioblastoma U87MG and U251MG cells, together with non-malignant SVG p12 cells, were used to evaluate the effects of isoliensinine on cell viability, apoptosis, PLCG1 signaling activity, second-messenger production, calcium homeostasis, mitochondrial function, and downstream survival pathways. Isoliensinine reduced glioblastoma cell viability and increased apoptotic cell death, accompanied by caspase activation and PARP cleavage, while showing comparatively lower cytotoxicity toward SVG p12 cells. Mechanistically, isoliensinine suppressed PLCG1 phosphorylation and reduced the production of inositol 1,4,5-trisphosphate and diacylglycerol, leading to impaired protein kinase C-related signaling, altered endoplasmic reticulum and mitochondrial calcium distribution, mitochondrial membrane potential loss, and activation of mitochondrial apoptotic responses. Functional restoration of PLCG1 activity and pharmacological rescue of diacylglycerol-responsive signaling attenuated isoliensinine-induced apoptotic signaling, supporting PLCG1 inhibition as an upstream event in the anti-glioblastoma activity of isoliensinine. These findings suggest that isoliensinine induces glioblastoma cell apoptosis by targeting PLCG1-mediated calcium and diacylglycerol signaling and provide a mechanistic basis for further evaluating this natural compound as a potential therapeutic candidate for glioblastoma.

PMID:
42874886
Bibliographic data and abstract were imported from PubMed on 15 Oct 2026.

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