TY - JOUR
T1 - Possible role of glutathione in mitochondrial apoptosis of human oral squamous cell carcinoma caused by inorganic selenium compounds
AU - Takahashi, Masato
AU - Sato, Tomonori
AU - Shinohara, Fumiaki
AU - Echigo, Seishi
AU - Rikiishi, Hidemi
PY - 2005/8/1
Y1 - 2005/8/1
N2 - Selenium (Sc) is a very effective anti-cancer agent. We studied the effects of inorganic Sc compounds on induction of apoptosis by which Se compounds exert cancer chemopreventive activity. With the use of HSC-3 human oral squamous cell carcinoma cells, the present study showed that treatment with Sc for 72 h, in the form of SeO2 and Na2SeO3, but not Na 2SeO4, markedly induced apoptosis in a dose-dependent manner. Treatment of HSC-3 cells with 100 μM SeO2 resulted in the caspasc-3-like and -9-like activation. Se compounds induced a loss of mitochondrial membrane potential (ΔΨm), but did not induce the generation of reactive oxygen species. Treatment with SeO2 for 18 h resulted in 80% loss of reduced glutathione (GSH), which is known to be involved in the metabolism of Sc. Treatment with N-acctyl-L-cysteinc, or exogenous GSH, prevented the SeO2-induced apoptosis. Treatment with GSH led to the partial reverse in reduction of ΔΨm caused by SeO2 while buthionine sulfoximine augmented the SeO2- or Na2SeO 3- induced apoptosis. These results suggest that modulation of the mitochondrial redox equilibrium by Se contributes to the mitochondrial pathway, regulating caspasc-9-mediated apoptosis without a concurrent increase in ROS.
AB - Selenium (Sc) is a very effective anti-cancer agent. We studied the effects of inorganic Sc compounds on induction of apoptosis by which Se compounds exert cancer chemopreventive activity. With the use of HSC-3 human oral squamous cell carcinoma cells, the present study showed that treatment with Sc for 72 h, in the form of SeO2 and Na2SeO3, but not Na 2SeO4, markedly induced apoptosis in a dose-dependent manner. Treatment of HSC-3 cells with 100 μM SeO2 resulted in the caspasc-3-like and -9-like activation. Se compounds induced a loss of mitochondrial membrane potential (ΔΨm), but did not induce the generation of reactive oxygen species. Treatment with SeO2 for 18 h resulted in 80% loss of reduced glutathione (GSH), which is known to be involved in the metabolism of Sc. Treatment with N-acctyl-L-cysteinc, or exogenous GSH, prevented the SeO2-induced apoptosis. Treatment with GSH led to the partial reverse in reduction of ΔΨm caused by SeO2 while buthionine sulfoximine augmented the SeO2- or Na2SeO 3- induced apoptosis. These results suggest that modulation of the mitochondrial redox equilibrium by Se contributes to the mitochondrial pathway, regulating caspasc-9-mediated apoptosis without a concurrent increase in ROS.
KW - Apoptosis
KW - Glutathione
KW - Mitochondria
KW - Oral squamous cell carcinoma
KW - Selenium
UR - http://www.scopus.com/inward/record.url?scp=33344471837&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33344471837&partnerID=8YFLogxK
M3 - Article
C2 - 16010432
AN - SCOPUS:33344471837
VL - 27
SP - 489
EP - 495
JO - International Journal of Oncology
JF - International Journal of Oncology
SN - 1019-6439
IS - 2
ER -