Activity of tumor necrosis factor-α blocked by phytoglycoprotein (38 kDa) at initiation stage in N-nitrosodiethylamine-induced ICR mice

Abstract

Hepatocellular carcinoma is becoming one of the most prominent types of cancer in the world. Recently, from Styrax japonica Siebold et al. Zuccarini (SJSZ), we isolated a glycoprotein which consists of carbohydrate moiety (52.64%) and protein moiety (42.35%). We evaluated whether SJSZ glycoprotein prevents hepatocarcinogenesis induced by N-nitrosodiethylamine (DEN). The purpose of this study was to evaluate the effect of SJSZ glycoprotein in DEN-induced hepatocarcinogenesis in ICR mice. To know chemopreventive effect of SJSZ glycoprotein on hepatocarcinogenesis, ICR mice were intraperitoneally injected with N-nitrosodiethylamine (DEN, 10 mg/kg) for 7 weeks. After sacrifice, we evaluated indicators of liver tissue damage [the activities of lactate dehydrogenase (LDH) and alanine aminotransferase (ALT), and thiobarbituric acid reactive substances (TBARS)], antioxidative enzymes [activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)], and initiating hepatocarcinogenic indicator [heat shock protein (HSP) 27 and 70] and hepatocarcinogenic signals [protein kinase C (PKC), extracellular signal-regulating kinase (ERK) 1/2, nuclear factor (NF)-κB (p50 and p65) and tumor necrosis factor-α (TNF-α)] using biochemical methods, immunoblot analysis, and RT-PCR. The results obtained from this study revealed that SJSZ glycoprotein (10 mg/kg, BW) decreased the levels of LDH, ALT, and TBARS, whereas the activities of SOD, GPx, and CAT increased in the DEN-induced ICR mice. With respect to the hepatocarcinogenic indicator and hepatocarcinogenic signals, HSP27, HSP70, PKC, ERK1/2, NF-κB (p50 and p65), and TNF-α, activity decreased. Hence, SJSZ glycoprotein might prevent expression of HSP27 and HSP70 by DEN.