TY - GEN
T1 - Oxidative upregulation of Bcl-2 in healthy lymphocytes
AU - Cristofanon, Silvia
AU - Nuccitelli, Silvia
AU - D'Alessio, Maria
AU - Radogna, Flavia
AU - De Nicola, Milena
AU - Bergamaschi, Antonio
AU - Cerella, Claudia
AU - Magrini, Andrea
AU - Diederich, Marc
AU - Ghibelli, Lina
PY - 2006/12
Y1 - 2006/12
N2 - In many cell systems, pharmacological glutathione (GSH) depletion with the GSH neosynthesis inhibitor buthionine sulfoximine (BSO) leads to cell death and highly sensitizes tumor cells to apoptosis induced by standard chemotherapeutic agents. However, some tumor cells upregulate Bcl-2 in response to BSO, thus surviving the treatment and failing to be chemosensitized. Cell lines of monocytic and lymphocytic origins respond to BSO treatment in an opposite way, lymphocytes being chemosensitized and unable to transactivate Bcl-2. In this article we investigate the response to BSO of lymphocytes freshly isolated from peripheral blood of healthy donors. After ensuring that standard separation procedures do not alter per se lymphocytes redox equilibrium nor Bcl-2 levels in the first 24 h of culture, we show that BSO treatment promotes the upregulation of Bcl-2, with a mechanism involving the increased radical production consequent to GSH depletion. Thus, BSO treatment may increase the differential cytocidal effect of cytotoxic drugs in tumor versus normal lymphocytes.
AB - In many cell systems, pharmacological glutathione (GSH) depletion with the GSH neosynthesis inhibitor buthionine sulfoximine (BSO) leads to cell death and highly sensitizes tumor cells to apoptosis induced by standard chemotherapeutic agents. However, some tumor cells upregulate Bcl-2 in response to BSO, thus surviving the treatment and failing to be chemosensitized. Cell lines of monocytic and lymphocytic origins respond to BSO treatment in an opposite way, lymphocytes being chemosensitized and unable to transactivate Bcl-2. In this article we investigate the response to BSO of lymphocytes freshly isolated from peripheral blood of healthy donors. After ensuring that standard separation procedures do not alter per se lymphocytes redox equilibrium nor Bcl-2 levels in the first 24 h of culture, we show that BSO treatment promotes the upregulation of Bcl-2, with a mechanism involving the increased radical production consequent to GSH depletion. Thus, BSO treatment may increase the differential cytocidal effect of cytotoxic drugs in tumor versus normal lymphocytes.
KW - Apoptosis
KW - Bcl-2
KW - Buthionine sulfoximine
KW - Glutathione
KW - Lymphocyte
UR - http://www.scopus.com/inward/record.url?scp=33947583288&partnerID=8YFLogxK
U2 - 10.1196/annals.1378.049
DO - 10.1196/annals.1378.049
M3 - Conference contribution
C2 - 17341597
AN - SCOPUS:33947583288
SN - 1573316474
SN - 9781573316477
T3 - Annals of the New York Academy of Sciences
SP - 1
EP - 9
BT - Signal Transduction Pathways, Part B
PB - Blackwell Publishing Inc.
ER -