An international research group coordinated by Sapienza biochemist Enzo Agostinelli is studying a new therapeutic application based on the high level of polyamines present in cancer cells as a source for cytotoxic metabolites through an interaction with specific metal enzymes belonging to the amino oxidase group.
The research group conducted studies on cancer cells from colon adenocarcinoma, as well as osteosarcoma, neuroblastoma and melanoma cultivations, all of which are multi-drug resistant and derive from extremely aggressive cancers, known for their high metastatic capacities and for their high resistance to cytotoxic agents. In fact, the level of polyamines (small polycations such as spermidine) and amino oxidases increases significantly in developing and cancerous tissues.
The study examined the high concentration of endogenous polyamines formed during cellular degenerative processes. The cytotoxic metabolites’ enzymatic formation of polyamines, hydrogen peroxide and aldehyde are responsible for the induced cytotoxicity on the cultivated cancer cells. This effect was not observed for normal cells such as melanocytes.
A recent publication on the International Journal of Oncology described how electronic microscopy imagery reveals how the obtained molecule is not only effective on cells damaged by melanoma, but also how it is extremely efficient in fighting cancer cells that have already treated with traditional chemotherapy methods that induce drug resistance.
"Our aim is to develop a therapy that prevents cancer patients from suffering the devastating side-effects often caused by current therapies," explains Enzo Agostinelli, "and to open new perspectives for those who suffer cells that develop a resistance to current drugs and therapies."
The anti-tumoural activity of the amino oxidase enzyme, following intraperitoneal administration in free form, encapsulated in liposomes, or conjugated with nanovector vesicles, was evaluated on the injected human tumour cells in immunosuppressed mice. The results provide great promise for the development of a new cancer therapy in which the polyamines, the amino oxidase and the products of their reaction become unexpected actors for a new cancer therapy strategy.
The International Foundation on Polyamines nominated Enzo Agostinelli, Professor of Biochemistry and Molecular Biology, as President following his intensive research in laboratories in the United States, Canada, Brazil, China, Japan, Taiwan, India, South Africa, Turkey, Russia and various EU countries, as well as his many scientific publications (over 130 contributions from articles and books published in prestigious international journals and more than 200 communications at national and international conferences).
Professor Agostinelli’s research has mainly focused on the identification of non-invasive cancer therapies based on the use of polyamines, aliphatic amines with a low molecular weight, which play an important role in the cell growth and differentiation.
The International Polyamine Foundation, which brings together leading experts from the international scientific community, will be headquartered at Sapienza University, underlining Italian excellence in this field of study and enhance the attractiveness of researchers from around the world who already work at Sapienza labs in the Physiology and Biochemistry Buildings.
"I am very pleased that the Foundation chose me as President and Sapienza University, in general. Pleased, but not surprised," explains Professor Agostinelli while he continues to assign tasks to the "Japanese Wakunaga Pharmaceutical Company" researchers on his team, "because Italian research is extremely advanced, recognized as influential in scientific fields and appreciated worldwide.”