Researchers find a substance that facilitates natural cell suppression in aggressive brain cancer

by Virginia Greco

A research team coordinated by Dr. Víctor J. Yuste of the Universitat Autònoma de Barcelona (UAB) demonstrated that the administration of a substance called “gossypol” to cells of glioblastoma, an incurable type of brain cancer, facilitates their death through the natural apoptosis mechanism. This study, in which took part members of the ICN2 Nanostructured Functional Materials Group, opens up a new avenue in the search for a treatment for glioblastoma.

Apoptosis is a natural mechanism by which defective cells induce their own death in order to preserve the health of the organism. It is a complex process, including many stages, in which the different parts of the cell gradually degrade. In cancer tissues, though, this mechanism is compromised so that, even when apoptosis begins, the process stops at one of the stages, letting the cell survive.

Thorough studies on how this process works and is altered are crucial to envision new therapies for cancer, in particular for some of the most aggressive and recurrent types, such as glioblastoma, a brain cancer for which a cure has not been found yet. It has been demonstrated that glioblastoma cells have insufficient levels of DFF40/CAD, a protein that, during apoptosis, orchestrates the breakdown of the cell nucleus. This shortage causes the fragmentation step not to complete and therefore the cell to survive and recover.

A paper published in Cancers presents a study coordinated by Dr. Víctor J. Yuste, professor at the Department of Biochemistry and Molecular Biology at the Faculty of Medicine (UAB) and researcher at the Institut de Neurociències of the UAB (INc-UAB), in which a substance derived from the cotton plant, gossypol, proves to be able to enhance the activity of DFF40/CAD. The researchers administered this molecule to the tumour cells and observed that, in the treated cells, the nuclear fragmentation process reached completion, resulting in cell death.

This study is the result of a close collaboration between researchers from various research centres in Catalonia (Spain): 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). Dr Daniel Ruiz Molina, leader of the ICN2 Nanostructured Functional Materials Group, and Dr Salvio Suárez-García, from the same group, participated in this work.

UAB’s press release: Activation of a key protein that allows glioblastoma cells to complete apoptosis

Image: Human glioblastoma cell treated with gossypol, observed through the freeze-fracture field emission-scanning electron microscopy (FE-SEM). [Credits: INc-UAB]

Reference 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. DOI: 10.3390/cancers13215579