Nitrosylated human serum albumin (SNO-HSA) induces apoptosis in tumor cells.
Recently, nitric oxide has been investigated as a potential anti-cancer therapy because of its cytotoxic activity. Previously, we found that S-nitrosylated human serum albumin (SNO-HSA) induced apoptosis in C26 cells, demonstrating for the first time that SNO-HSA has potential as an anti-cancer drug. In the present study, the anti-tumor activity of SNO-HSA in another tumor type of cancer cell was investigated using murine tumor LY-80 cells. Mitochondrial depolarization, activation of caspase-3 and DNA fragmentation were induced in LY-80 cells by SNO-HSA treatment in a dose-dependent manner. Inhibition of caspase activity resulted in complete inhibition of DNA fragmentation induced by SNO-HSA. The cytotoxic effects of SNO-HSA on LY-80 were concentration-dependent. Tumor growth in LY-80-tumor-bearing rats was significantly inhibited by administration of SNO-HSA compared with saline- and HSA-treatment. These results suggest that SNO-HSA has potential as a chemopreventive and/or chemotherapeutic agent because it induces apoptosis in tumor cells.
Katayama
Naohisa
N
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
Nakajou
Keisuke
K
Ishima
Yu
Y
Ikuta
Shotaro
S
Yokoe
Jun-ichi
J
Yoshida
Fumika
F
Suenaga
Ayaka
A
Maruyama
Toru
T
Kai
Toshiya
T
Otagiri
Masaki
M
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000633:toxicity; D009603:Nitroso Compounds / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000494:pharmacology*; D000075462:Serum Albumin, Human
D000970:Antineoplastic Agents; D009603:Nitroso Compounds; C511514:S-nitrosoalbumin, human; D012709:Serum Albumin; D009569:Nitric Oxide; D053148:Caspase 3; D000075462:Serum Albumin, Human