JSI-124 Induces Cell Cycle Arrest and Regulates the Apoptosis in Glioblastoma Cells

Cucurbitacin I (JSI-124), derived from Cucurbitaceae, has shown the potential to induce apoptosis and cell cycle arrest in some cancer cells. However, the effect of JSI-124 on glioblastoma multiforme (GBM) cell cycle and apoptosis is still unclear. Our investigation revealed that JSI-124 effectively reduced cell viability in GBM cells, leading to apoptosis and increased caspase-3 activity. Intriguingly, JSI-124 caused the accumulation of G2/M phase to regulate cell cycle, confirmed by MPM-2 staining and increased protein synthesis during mitosis by mitotic index analysis. Western blot analysis found that JSI-124 affected the progression of G2/M arrest by downregulating the CDK1 and upregulating the cyclinB1, suggesting that JSI-124 disrupted the formation and function of the cyclin B1/CDK1 complex in GBM8401 and U87MG cells. However, we found the JSI-124-regulated cell cycle G2/M and apoptosis-relative gene in GBM8401 and U87MG cells by NGS data analysis. Notably, we found that the GBM8401 and U87MG cells observed regulation of apoptosis and cell-cycle-related signaling pathways. Taken together, JSI-124 exhibited the ability to induce G2/M arrest, effectively arresting the cell cycle at critical stages. This arrest is accompanied by the initiation of apoptosis, highlighting the dual mechanism of action of JSI-124. Collectively, our findings emphasize that JSI-124 holds potential as a therapeutic agent for GBM by impeding cell cycle progression, inhibiting cell proliferation, and promoting apoptosis. As demonstrated by our in vitro experiments, these effects are mediated through modulation of key molecular targets.

Automated summary

Cucurbitacin I (JSI-124) derived from Cucurbitaceae has the potential to induce apoptosis and cell cycle arrest in glioblastoma multiforme (GBM) cells. JSI-124 effectively reduced cell viability in GBM cells, leading to apoptosis and cell cycle arrest.