PSA-activated proaerolysin as a prostate specific cancer therapy

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dc.contributor.author Abi-Habib, Ralph
dc.contributor.author Browning, Jeff L.
dc.contributor.author Singh, Ravibhushan
dc.contributor.author Carter, Carol
dc.contributor.author Ortiz, Janelle
dc.date.accessioned 2018-06-18T09:52:34Z
dc.date.available 2018-06-18T09:52:34Z
dc.date.copyright 2006 en_US
dc.identifier.uri http://hdl.handle.net/10725/8051
dc.description.abstract Native proaerolysin is a channel-forming bacterial protoxin that is activated upon cleavage by host proteases such as furin. PRX302 is an engineered form of proaerolysin in which the furin cleavage site has been replaced with a sequence known to be preferred by the protease, prostate specific antigen (PSA). The goal of this study was to examine the suitability of PRX302 for use as a therapeutic agent in prostate cancer and benign prostatic hyperplasia as assessed by comparing proteolytic activation of PRX302 and native proaerolysin and their cytotoxicity towards PSA-producing and non-producing cell lines. Modification of native proaerolysin to PRX302 markedly altered the activity of each of the proteases (chymotrypsin, trypsin, furin, and thrombin) tested toward this protein. Activity toward proaerolysin was decreased 10-100 fold for each of the proteases tested except PSA, which showed a 4-fold increase in activity against the modified protein. Of all enzymes tested, only PSA cleaved more PRX302 than proaerolysin. Indeed the ratio of PRX302 to proaerolysin cleavage by PSA was more than 40 times that of any other protease tested. As expected, native proaerolysin was effectively cytotoxic at low pM concentrations in all cells tested (LNCaP, DU145, CWR22Rvi, PC3, PrEC, and RWPE2-W99). However, PRX302 was cytotoxic at low pM concentration only in normal (PrEC) and papilloma- transfected (RWPE2-W99) prostate cells, both of which produce active PSA. In conclusion, PRX302 appears to be preferentially activated by PSA and selectively kills PSA producing cells. PRX302 deserves further study for possible treatment of prostate cancer and benign prostatic hyperplasia. en_US
dc.language.iso en en_US
dc.title PSA-activated proaerolysin as a prostate specific cancer therapy en_US
dc.type Conference Paper / Proceeding en_US
dc.author.school SAS en_US
dc.author.idnumber 200901419 en_US
dc.author.department Natural Sciences en_US
dc.description.embargo N/A en_US
dc.identifier.ctation Browning, J. L., Abi-Habib, R., Singh, R., Carter, C., Ortiz, J., Merchant, R., ... & Frankel, A. E. (2006). PSA-activated proaerolysin as a prostate specific cancer therapy. en_US
dc.author.email ralph.abihabib@lau.edu.lb en_US
dc.conference.pages 514 en_US
dc.conference.title Proceeding of the American association of cancer research en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php en_US
dc.identifier.url http://cancerres.aacrjournals.org/content/66/8_Supplement/514.4.short en_US
dc.publication.date 2006 en_US
dc.volume 47 en_US
dc.author.affiliation Lebanese American University en_US

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