Cajaninstilbene acid induced apoptosis and cell cycle arrest in glioblastoma multiforme through mitochondrial...

Glioblastoma (GBM) is a highly aggressive primary brain tumor with a poor prognosis and high mortality rate. Cajaninstilbene acid (CSA), a bioactive compound derived from pigeon pea leaves, has been reported to exhibit diverse biological activities, including potential anticancer properties. Given its dietary origin, understanding the cytotoxic effects and mechanisms of CSA is essential for food safety assessment. In this study, we investigated the cytotoxic mechanisms of CSA in GBM cell lines (LN229 and U87) and a xenograft mouse model. Our results showed that CSA significantly suppressed GBM cell proliferation, induced G2/M phase arrest, and activated caspase-dependent apoptosis. Network pharmacology analysis identified the MAPK signaling pathway as a key mediator of CSA-induced cytotoxicity. Importantly, CSA-induced effects on apoptosis, cell cycle arrest, and cell migration were markedly attenuated by the p38-specific inhibitor SB203580. Further mechanistic studies revealed that CSA-induced p38 phosphorylation dependent on mitochondrial reactive oxygen species (mtROS) production, which was completely reversed by the antioxidant N-acetyl-l-cysteine (NAC). Finally, CSA effectively suppressed tumor growth in a mouse xenograft model without causing significant body weight loss or histopathological toxicity in major organs. Collectively, these findings highlight the cytotoxic mechanism of CSA in GBM cells and provide a basis for its safety evaluation.