title: The antioxidant phenylaminoethyl selenide reduces doxorubicin-induced cardiotoxicity in a xenograft model of human prostate cancer.
abstract: Anthracyclines are potent anticancer agents, but cardiotoxicity mediated by free radical generation limits their clinical use. This study evaluated the anticancer activity of phenyl-2-aminoethyl selenide (PAESe) and its potential to reduce doxorubicin (DOX)-induced cardiotoxicity. Growth inhibitory effects of PAESe with DOX, and vincristine, clinically used anticancer agents, and tert-butylhydroperoxide (TBHP), a known oxidant, on the growth of human prostate carcinoma (PC-3) cells was determined. PAESe (≤1μm) did not alter the growth of PC-3 cells, however, concomitant use of PAESe decreased the oxidative-mediated cytotoxicity of TBHP, but had limited effect on vincristine or DOX activity. Further, PAESe decreased the formation of intracellular reactive oxygen species from TBHP and DOX. The effect of PAESe on the activity of DOX was determined using a tumor (PC-3) xenograft model in mice. PAESe did not alter DOX antitumor activity and showed evidence of direct antitumor activity relative to controls. DOX treatment decreased mice body weight significantly, whereas concomitant administration of PAESe and DOX was similar to controls. Most importantly, PAESe decreased DOX-mediated infiltration of neutrophil and macrophages into the myocardium. These data suggest PAESe had in vivo antitumor activity and in combination with DOX decreased early signs of cardiotoxicity while preserving its antitumor activity.
authors: Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602, United States.
authors: Jeong Yeon
authors: JY
authors: Kang
authors: Leah J
authors: LJ
authors: Costyn
authors: Tamas
authors: T
authors: Nagy
authors: Elizabeth A
authors: EA
authors: Cowan
authors: Charlie D
authors: CD
authors: Oldham
authors: Sheldon W
authors: SW
authors: May
authors: Robert D
authors: RD
authors: Arnold
mesh_terms: D000814:Aniline Compounds / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D002460:Cell Line; D004317:Doxorubicin / Q000494:pharmacology* / Q000627:therapeutic use*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D000975:Antioxidants; D004317:Doxorubicin