Study of nitric oxide in metastasis and therapeutic potential of BPP-10c (Bj-PRO-10c) on cancer treatment

• Grant number: 17/05629-5
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): May 01, 2017
• Effective date (End): April 30, 2019
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Claudiana Lameu
• Grantee: Rodrigo Lopes Seeger
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 15/19128-2 - Metastasis mechanisms of childhood tumors to bone marrow, AP.JP

Abstract

Nitric oxide (NO) was first described as a secondary messenger that regulates vasodilator signaling in the cardiovascular system. However, in recent years other important functions performed by NO from physiological functions to functions in human pathologies have been characterized. Among these, the regulation of the formation, progression and metastasis development of various forms of cancer. NO is synthesized from L-arginine and oxygen by a family of enzymes named nitric oxide synthases (NOS). The three isoforms of NOS, inducible (iNOS), endothelial (eNOS) and neuronal (nNOS) are significantly important in the cancer study, since it has been demonstrated alterations in the expression of different NOS isoforms in different forms of cancer and affecting in a heterogeneous way the neoplastic cells and it can not easily classified as pro-metastatic or anti-metastatic. Recently, it has been shown that some antihypertensive peptides isolated from Bothrops jararaca venom, the BPPs, induce the production of nitric oxide (NO). Bj-PRO-10c was the peptide of the BPP family with the best characterized mechanism of NO production. This peptide increases the levels of L-arginine due to the activation of argininosuccinate synthase (ASS), a step-limiting enzyme in the biosynthesis of L-arginine in the citrulline-NO cycle for NO production. Therefore, this decapeptide will be used in this project as a tool to clarify the role of NO in tumor progression and neuroblastoma cell metastasis. As well as to understand the mechanism the nitrergic system in the regulation of metastasis. The potential therapeutic applications of Bj-PRO-10c regulating the activity and expression of the enzyme ASS also will be evaluated on the treatment of cancer and metastasis. Several papers report a negative correlation between the expression of ASS and the development of metastasis in several cancer types. Therefore, we expect Bj-PRO-10c to reverse the metastatic potential of neuroblastoma due to activation and induction of enzyme expression in tumor cells. (AU)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SEEGER, Rodrigo Lopes. The role of nitric oxide in the therapeutic potential of BPP-10c for the treatment of cancer-associated diseases. 2019. Master's Dissertation - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.