Cancer cells have many ways to deal with apoptosis, programmed cell death the means by which organisms deal with defective cells. One such defense is to produce quantities of phosphatic acid, a phospholipid constituent of cellular membranes.
However, phosphatidic acid, unlike other phospholipids, also acts as a signaling molecule for cells promoting cellular growth and preventing apoptosis.
The researchers have now shown that phosphatidic acid may act as a target molecule for novel anti-cancer drugs.
Siramesine is a drug molecule developed and synthesized by Lundbeck A/S for the treatment of anxiety. Its development was discontinued due to unsatisfying efficacy in clinical trials in 2002.
Later professor Marja Jaattela and co-workers at the Danish cancer institute discovered that siramesine effectively inhibits the growth of both cultured cancer cells as well as solid tumors in mice.
Siramesine is known to bind sigma-receptors, the physiological role of which remains unknown, on the cellular surface and this interaction was also believed to underlie its anti-tumor actions.
Led by Professor Paavo Kinnunen, the researchers studied the interaction of this drug with different phospholipids using biophysical methods and different model cellular membranes.
Also, a computer simulation was performed as collaboration with MEMPHYS, Odense, Denmark, to further their understanding of this interaction.
"The key finding of our study was that siramesine avidly and specifically binds to phosphatidic acid", said MD Mikko Parry from Helsinki Biophysics and Biomembrane group at the Institute of Biomedicine, University of Helsinki.
He added: "Importantly, this is the first time it's shown that a lipid second messenger can act as a drug target: it is a totally new mechanism of action and constitutes a novel paradigm for developing new, more effective anti-cancer drugs."