8th January 2013 - Researchers Identify A New Class Of Drugs, Capable Of Inhibiting The Proliferation Of Various Cancer Cells
Discovered the capability of some molecules of inhibiting the activity of acid ceramidase, a protein involved in the proliferation of malignant cells in cancers such those of the skin, colon, prostate and breast.A pharmacological intervention directed against the proliferation of cancer cells is at the centre of a study conducted by researchers of the Drug Discovery and Development (D3) department of the Istituto Italiano di Tecnologia (IIT), based in Genoa (Italy), published on the International journal Scientific Reports, with the title "Discovery of highly potent acid ceramidase inhibitors with in vitro tumor chemosensitizing activity". The results show the inhibitory action of new drugs on the activity of acid ceramidase, a protein that increases the aggressiveness of cancer cellsand favours their resistance to chemotherapeutic agents and radiotherapy.
The research has been coordinated by Prof. Daniele Piomelli, Director of the Drug Discovery and Development department of the Istituto Italiano di Tecnologia, with the participation of researchers of the University of California - Irvine and the University of Modena and Reggio Emilia (Italy).
Acid ceramidase is an enzyme that regulates the quantity of ceramide, an important lipid messenger, involved in the control of cell proliferation and death. An increase in the activity of this enzyme causes a reduction of ceramide levels, which results in the acceleration of the growth of cancer cells and raises its resistance capabilities. This is often observed in human cancers, such as various types of skin, colon, prostate and breast cancers.
«Our aim was to identify a new class of drugs capable of inhibiting acid ceramidase, strongly and selectively, to weaken cancer cells and increase the effectiveness of the available therapies. – comments Prof. Piomelli – This sensitizing action can be of great help, especially in the case of those patients who develop a resistance to chemotherapeutic agents and radiotherapy, a condition which arises, unfortunately, very frequently».
The starting point of this study was a compound called Carmofur, used in the clinical treatment of colon cancers, of which the mechanism of action was unknown. «We discovered that Carmofur is a strong inhibitor of acid ceramidase and that this action is at the origin of its antitumor effect. – explains Dr. Natalia Realini, researcher of the D3 department and first author of the study – Starting from this observation, we created a series of new molecules, demonstrating that they are capable of strengthening the action of chemotherapeutic drugs, in cultures of human cancer cells. It is important to remember that these are the first molecules capable of inhibiting in such a strong way acid ceramidase, both in vitro and in vivo».
The next steps will be of optimizing, on a chemical level, the action of the new inhibitors, increasing their selectivity, safety and method of administration