Activation of a key protein that allows glioblastoma cells to complete apoptosis

A research team coordinated from the Universitat Autònoma de Barcelona (UAB), with the participation of Judit Ribas, lecturer at the University of Lleida and head of the IRBLleida Pharmacology Unit research group, describes how a substance called gossypol primes glioblastoma cells, an incurable type of brain cancer, to be eliminated by apoptosis. The results open up a new line of research in the development of new treatments for this type of cancer.

Apoptosis is the mechanism by which defective cells promote their own death to protect the body. It is a complex process, with many stages, in which the different parts of the cell gradually degrade. In glioblastoma cells, even when apoptosis begins, the process stops at one of the stages and allows the cell to survive.

In previous studies, researchers had already demonstrated that glioblastoma cells have insufficient levels of DFF40/CAD, a protein that, during apoptosis, orchestrates the breakdown of the cell nucleus. This shortage means that the fragmentation step is not completed and the cell can recover.

In this article, published in Cancers and coordinated by Dr. Víctor J. Yuste, professor at the Department of Biochemistry and Molecular Biology at the UAB Faculty of Medicine and researcher at the Institut de Neurociències of the UAB (INc-UAB), the researchers administered to the tumor cells a substance derived from the cotton plant, gossypol. This molecule enhances the activity of DFF40/CAD. The result is that, in the treated cells, the nuclear fragmentation process is completed and the cell dies.

Dr. Laura Martinez-Escardó, researcher at the Department of Biochemistry and Molecular Biology of the UAB and first author of the work explains the finding: "We have seen that, contrary to other drugs, gossypol allows DFF40/CAD to stay in the nucleus for longer to promote its fragmentation. With our study, we demonstrated that compounds such as gossypol can push these cells to a point of no return after starting the cell death process without modifying them genetically".

The future of this research is promising as explained by Dr. Yuste: "Promoting apoptosis to end properly in tumor cells could be a good therapeutic strategy to treat glioblastoma. The findings presented are promising and encourage us to carry out further research. The new results help us better understand the biology of this aggressive tumor and may provide us with new tools for the development of more effective strategies. This is especially interesting because there is currently no cure for this disease."

This study is the result of a close collaboration between basic and clinical research. Dr. Víctor J. Yuste has led a multidisciplinary team of basic researchers, neuro-oncologists, pathologists and neurosurgeons, from the UAB, the Bellvitge University Hospital (HUB)-Bellvitge Biomedical Research Institute (IDIBELL), the Catalan Institute of Oncology (ICO), the Catalan Institute of Nanoscience and Nanotechnology (ICN2), and the Lleida Biomedical Research Institute (IRBLleida). This research has been funded by the Ministry of Science and Innovation, and co-financed by the ERDF fund "a way of making Europe".

Original article:
Martínez-Escardó L, Alemany M, Sánchez-Osuna M, Sánchez-Chardi A, Roig-Martínez M, Suárez-García S, Ruiz-Molina D, Vidal N, Plans G, Majós C, Ribas J, Baltrons MA, Bayascas JR, Barcia C, Bruna J, Yuste VJ. Gossypol Treatment Restores Insufficient Apoptotic Function of DFF40/CAD in Human Glioblastoma Cells Cancers. 2021; 13(21):5579. https://doi.org/10.3390/cancers13215579

Information: Communication Universitat Autònoma de Barcelona