Scientists Identify a Dependency of Glioblastoma on Biotin

The FDA-approved anti-fungal drug, sulconazole, exhibits anti-cancer properties towards glioblastoma cells.

Sulconazole, an anti-fungal drug exhibits anti-cancer properties towards glioblastoma cells, as per the study published in the Science Advances.

Glioblastoma is the most fatal malignant adult brain cancer that may arise from neuroglial stem or progenitor cells. Few mutations or those with a known history of other cancers and radiation therapy may predispose patients to develop brain cancer.

‘New discovery lays foundation for the development of drug combinations from existing or new small molecule inhibitors against the biotin-dependent metabolic enzymes for treating glioblastoma.’
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This compound found to compete with biotin (Vitamin H), allowing it to inhibit the normal function of biotin-dependent metabolic enzymes and specific histone modification-associated gene expression.

This compromises glioblastoma metabolism and epigenetics, thereby impairing the tumour growth and invasiveness of glioblastoma cells.

In mammalian cells, holocarboxylase synthetase, or HLCS, is the enzyme that serves to distribute biotin to the biotin-dependent proteins. Gene silencing of HLCS reduces the glioblastoma’s tumorigenicity in mouse models.

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Glioblastomas are tumors that arise from astrocytes that make up the supportive tissue of the brain. Glioblastomas are usually highly malignant.

High HLCS expression is linked to glioblastoma and inferior glioma patient outcome. While HLCS is present in healthy patients, its expression increases in the tumours of glioblastoma patients.

Glioblastoma cells with higher HLCS expression could get better supply of biotin to the biotin-dependent metabolic enzymes and histones, which results in a more proliferative and invasive glioblastoma.

So, the dependency of glioblastoma on biotin distribution suggests that the rational co-targeting of biotin-dependent metabolism and epigenetic pathways may be explored for glioblastoma eradication.

“Since biotin is found in various food sources, including legumes, egg yolk and offal, and commonly consumed as a supplement, these findings raise an important consideration of regulating biotin consumption in glioblastoma patients.

This discovery would also lay the foundation for the development of drug combinations from existing or new small molecule inhibitors against some of the biotin-dependent metabolic enzymes and histone modifications to cripple glioblastoma; some of these are already being actively explored in cancer treatment,” said Assistant Professor Derrick Ong from the Department of Physiology and Principal Investigator of this study.

Source-Medindia