Cucurbitacin B suppresses glioblastoma via the STAT3/ROS/endoplasmic reticulum stress pathway

TL;DR

Cucurbitacin B, a natural compound, shows promise in treating glioblastoma by triggering cell death and improving drug delivery through a new liposome-based method.

Contribution

A novel liposome formulation enhances CuB delivery to brain tumors, revealing its therapeutic potential via the STAT3/ROS/ER stress pathway.

Findings

CuB induces GBM cell apoptosis through the STAT3/ROS/endoplasmic reticulum stress pathway.

M@CuB-Lips improves targeted drug delivery to brain tumors and enhances tumor inhibition.

The formulation promotes effector T-cell infiltration in glioblastoma models.

Abstract

Cucurbitacin B (CuB), the tetracyclic triterpenoid compound belonging to cucurbitaceae family, demonstrates significant anticancer properties across various tumor types. However, its efficacy against glioblastoma (GBM), particularly in overcoming blood-brain barrier (BBB) and unique tumor microenvironment, remains a critical area of investigation. Our study reveals that CuB causes GBM cell apoptosis via STAT3/ROS/endoplasmic reticulum (ER) stress pathway. To enhance targeted delivery, we developed M@CuB-Lips, a novel formulation of CuB encapsulated in cancer cell membrane-coated liposomes. In vitro and in vivo experimental results verified targeted M@CuB-Lips delivery to brain tumor sites, demonstrating significant tumor inhibition and enhanced effector T-cell infiltration. These findings underscore CuB’s potential in GBM therapy, particularly through STAT3 suppression and ROS-ER Stress pathway activation, while M@CuB-Lips offers a promising strategy for targeted drug delivery.

The online version contains supplementary material available at 10.1038/s41598-025-21526-0.

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