Aminoguanidine: An attractive line as a multi-modal avenue to overcome tumor

March 09, 2009

Aminoguanidine is a compound that exerts multiple biological actions. Aminoguanidine has well described antioxidant properties and is also an inhibitor of nitric oxide synthases, the enzymes that produce nitric oxide. The nitric oxide molecule has been implicated in different biological processes associated with both survival and cell death. In vitro, nitric oxide exhibits cytostatic or cytotoxic effects in cancer cells according to its concentration within the tumor microenvironment. Although the in vitro action of nitric oxide synthase inhibitors (such as aminoguanidine) has been extensively studied in tumor cells, little research has been undertaken as regards their in vivo effects on cancer growth. Pancreatic cancer is a lethal disease due to its aggressive nature and lack of response to conventional therapy. New therapeutic modalities are keenly sought.

A research article, to be published on March 7, 2009 in the World Journal of Gastroenterology, addresses this question. This research team, led by Professor Gabriela Martín from the Laboratory of Radioisotopes, School of Pharmacy and Biochemistry, University of Buenos Aires, has carried out investigations in cancer biology on the role of histamine and other growth factors in cell proliferation, differentiation and death, and also in tumor progression, for more than ten years They have demonstrated that histamine exerts an antiproliferative effect in different human neoplastic cell lines with NO probably being involved in this action. Various publications have shown the in vitro action of nitric oxide synthase inhibitors (such as aminoguanidine), the article further investigate the role of aminoguanidine in the in vivo pancreatic cancer growth.

Human pancreatic cancer xenografted mice were employed for the study. Aminoguanidine treatment reduced the growth of xenografted tumors in mice, delayed the appearance of metastases, and enhanced survival.

Aminoguanidine showed an anti-tumoral action evidenced by a lower tumor volume at the end of treatment, a delayed appearance of palpable metastases and an extended life span. The antiproliferative action was associated with a lower expression of endothelial nitric oxide synthase, a reduced NO production, an antiangiogenic effect and also reduced expression of antioxidant enzymes. This is the first study reporting beneficial effects induced by aminoguanidine in pancreatic cancer.

Chemoresistance is still the major problem of anticancer drug treatment of malignant diseases, such as pancreatic carcinoma. In this sense, aminoguanidine could provide an attractive line of investigation as a multi-modal avenue to overcome the illness due to its different effects on tumor biology.

World Journal of Gastroenterology

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