TY - JOUR
T1 - Antioxidant-prooxidant properties of a new organoselenium compound library
AU - Plano, Daniel
AU - Baquedano, Ylenia
AU - Ibánez, Elena
AU - Jiménez, Iosu
AU - Palop, Juan Antonio
AU - Spallholz, Julian E.
AU - Sanmartín, Carmen
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2010/10
Y1 - 2010/10
N2 - The present study describes the biological evaluation of a library of 59 organoselenium compounds as superoxide (O2-) generators and cytotoxic agents in human prostate cancer cells (PC-3) and in breast adenocarcinoma (MCF-7). In order to corroborate that the biological activity for selenium compounds depends on the chemical form, a broad structural variety is presented. These structures include selenocyanates, diselenides, selenoalkyl functional moieties and eight newly synthesized symmetrically substituted dithioselenites and selenylureas. Eleven of the derivatives tested showed high levels of superoxide generation in vitro via oxidation of reduced glutathione (GSH) and nine of them were more catalytic than the reference compound, diselenodipropionic acid. Eighteen of the library compounds inhibited cell growth more than or similar to reference chemotherapeutic drugs in PC-3 and eleven were more potent cytotoxic agents than etoposide in the MCF-7 cell line. Considering both parameters (superoxide generation and cell cytotoxicity) compounds B1, C6 and C9 displayed the best therapeutic profiles. Considering that many diselenide compounds can generate superoxide (O2 -) in vitro via oxidation of GSH and other thiols, the analogue B1, that contains a diselenide moiety, was selected for a preliminary mechanistic investigation, which . revealed that B1 has apoptogenic effects similar to camptothecin mediated by reactive oxygen species (ROS) in lymphocytic leukemia cells (CCRF-CEM) and affected the MCF-7 cell-cycle in G2/M and S-phases.
AB - The present study describes the biological evaluation of a library of 59 organoselenium compounds as superoxide (O2-) generators and cytotoxic agents in human prostate cancer cells (PC-3) and in breast adenocarcinoma (MCF-7). In order to corroborate that the biological activity for selenium compounds depends on the chemical form, a broad structural variety is presented. These structures include selenocyanates, diselenides, selenoalkyl functional moieties and eight newly synthesized symmetrically substituted dithioselenites and selenylureas. Eleven of the derivatives tested showed high levels of superoxide generation in vitro via oxidation of reduced glutathione (GSH) and nine of them were more catalytic than the reference compound, diselenodipropionic acid. Eighteen of the library compounds inhibited cell growth more than or similar to reference chemotherapeutic drugs in PC-3 and eleven were more potent cytotoxic agents than etoposide in the MCF-7 cell line. Considering both parameters (superoxide generation and cell cytotoxicity) compounds B1, C6 and C9 displayed the best therapeutic profiles. Considering that many diselenide compounds can generate superoxide (O2 -) in vitro via oxidation of GSH and other thiols, the analogue B1, that contains a diselenide moiety, was selected for a preliminary mechanistic investigation, which . revealed that B1 has apoptogenic effects similar to camptothecin mediated by reactive oxygen species (ROS) in lymphocytic leukemia cells (CCRF-CEM) and affected the MCF-7 cell-cycle in G2/M and S-phases.
KW - Cytotoxicity
KW - Diselenodipropionic acid
KW - Selenium
KW - Superoxide
UR - http://www.scopus.com/inward/record.url?scp=78149456914&partnerID=8YFLogxK
U2 - 10.3390/molecules15107292
DO - 10.3390/molecules15107292
M3 - Article
C2 - 20966875
AN - SCOPUS:78149456914
VL - 15
SP - 7292
EP - 7312
JO - Molecules
JF - Molecules
SN - 1420-3049
IS - 10
ER -