Researchers in Finland, Sweden, and Switzerland have shown how the most aggressive form of brain cancer, glioblastoma, can be stopped in its tracks by an antihistamine drug that triggers a form of cell death caused by leaky lysosomes. Though this was a mouse study as most initial studies are, it is very promising. Headed by Pirjo Laakkonen, PhD, at the University of Helsinki, the studies demonstrated an association between the fatty acid binding protein – mammary-derived growth inhibitor (MDGI) and poorer prognosis in patients.
MDGI shuttles fatty acids into cells where they, among other things, become integral components of lysosomal membranes. Lysosomes are little organelles inside our cells that contain numerous digestive enzymes that remove waste and recycle worn-out cellular parts to help keep a cell alive. Healthy lysosomal membranes enclose these enzymes and release them inside the cell only when necessary. If we could destabilize these membranes, we could spill the content of the lysosomes (the digestive enzymes) into the cell and essentially stimulate apoptosis (cell death).
The study focused on Glioblastoma, one of the most aggressive brain cancers we face. The team’s studies found that blocking the MDGI gene (thereby NOT allowing fatty acids into the cell as readily) in glioblastoma cell lines disrupted fatty acid transport into cells and their incorporation into lysosomal membranes, which compromised lysosomal membrane composition and integrity, resulting in lysosomal membrane permeabilization (LMP). LMP is an intracellular cell death pathway triggered when the lysosome contents leak into the cell. The team’s subsequent studies in cell lines and in live mice found that treatment with the anti-histamine Clemastine (Dayhist, Dayhist Allergy, and Allergy Relief), an older type of antihistamine that can cross the blood-brain barrier, effectively mirrored the effects of MDGI, triggering LMP and causing glioblastoma cell death, without harming healthy cells.
In non-brain tumors where crossing the blood-brain barrier is not an issue, theory may admit that any anti-histamine, drug or natural histamine blockers, may illicit the same response in many tumors. Should all cancer patients go on anti-histamine medications or histamine blocking nutrients? That remains to be answered with more studies but this looks very promising!
Through further experiments the investigators showed that MDGI was essential to glioma cell survival. Glioma cells engineered to overexpress MDGI also grew more aggressively and invasively than non-engineered tumor cells following implantation into experimental mice. Conversely, silencing the MDGI gene dramatically reduced the viability of patient-derived glioma cells and blocked cell proliferation. Human glioblastoma cells lacking MDGI were also unable to form tumors when transplanted into mice. “These results demonstrate a dose-dependent effect of MDGI silencing on glioblastoma cell growth and viability.”