title: Matrix metalloproteinase-2 and -9 in glioblastoma: a trio of old drugs-captopril, disulfiram and nelfinavir-are inhibitors with potential as adjunctive treatments in glioblastoma.
abstract: Given the poor prognosis of glioblastoma, we have been investigating treatments adjunctive to the current standard of resection, irradiation and temozolomide. Our focus has been on exploring already-marketed medicines that have evidence of inhibiting growth factors previously identified as active and important in glioblastoma. In this short note we describe how previous research has demonstrated that the common angiotensin-converting enzyme (ACE) inhibitor captopril used to treat hypertension and for renal protection inhibits 72-kDa matrix metalloproteinase-2 and 92-kDa matrix metalloproteinase-9, which a separate body of research shows are used by glioblastoma cells to grow and invade. We review these bodies of data and combine them to conclude that captopril may slow glioblastoma progression. Two other drugs, the aldehyde dehydrogenase inhibitor disulfiram used to treat alcoholism and the anti-HIV protease inhibitor nelfinavir also have a database supporting their incidental inhibition of matrix metalloproteinases. Given the importance of matrix metalloproteinases in helping glioblastomas grow and invade, we suggest that this trio-captopril, disulfiram, and nelfinavir-be tested for antiglioblastoma activity.
authors.affiliation: Department of Psychiatry, University of Vermont, Burlington, USA. richarderickast@gmail.com
authors.forename: Richard E
authors.initials: RE
authors.lastname: Kast
authors.forename: Marc-Eric
authors.initials: ME
authors.lastname: Halatsch
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D002216:Captopril / Q000494:pharmacology / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D004221:Disulfiram / Q000494:pharmacology / Q000627:therapeutic use; D005909:Glioblastoma / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D019888:Nelfinavir / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D002216:Captopril; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D019888:Nelfinavir; D004221:Disulfiram