Plant‐originated glycoprotein (24 kDa) has an inhibitory effect on proliferation of BNL CL.2 cells in response to di(2‐ethylhexyl)phthalate

Abstract

Di(2-ethylhexyl)phthalate (DEHP) is one of the many environmental chemicals that are widely used in polyvinyl chloride products, vinyl flooring, food packaging and infant toys. They cause cell proliferation or dysfunction of human liver. The purpose of this study is to investigate the inhibitory effect of a glycoprotein (24 kDa) isolated from Zanthoxylum piperitum DC (ZPDC) on proliferation of liver cell in the DEHP-induced BNL CL. 2 cells. [³H]-thymidine incorporation, intracellular reactive oxygen species (ROS), intracellular Ca²⁺ mobilization and activity of protein kinase C (PKC) were measured using radioactivity and fluorescence method respectively. The expression of mitogen-activated protein kinases [extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK)], activator protein (AP)-1 (c-Jun and c-Fos), proliferating cell nuclear antigen (PCNA) and cell cycle-related factors (cyclin D1/cyclin-dependent kinase [CDK] 4) were evaluated using Western blotting or electrophoretic mobility shift assay. The results in this study showed that the levels of [³H]-thymidine incorporation, intracellular ROS, intracellular Ca²⁺ mobilization and activity of PKCα were inhibited by ZPDC glycoprotein (100 µg/ml) in the DEHP-induced BNL CL. 2 cells. Also, activities of ERK, JNK and AP-1 were reduced by ZPDC glycoprotein (100 µg/ml). With regard to cell proliferation, activities of PCNA and cyclin D1/CDK4 were significantly suppressed at treatment with ZPDC glycoprotein (100 µg/ml) in the presence of DEHP. Taken together, these findings suggest that ZPDC glycoprotein significantly normalized activities of PCNA and cyclin D1/CDK4, which relate to cell proliferation factors. Thus, ZPDC glycoprotein appears to be one of the compounds derived from natural products that are able to inhibit cell proliferation in the phthalate-induced BNL CL. 2 cells.

Di (2-ethylhexyl) phthalate inhibits growth of mouse ovarian antral follicles through an oxidative stress pathway

“…Previous studies indicate that both AREs and motifs for NF-κB and AP-1 are present in the promoter regions of most of the antioxidant enzymes, including SOD1, SOD2, CAT and GPX (Banning et al , 2005; Scandalios, 2005). Interestingly, numerous studies have shown that DEHP induces oxidative stress and causes apoptosis in hepatocytes by activating ERK/MAPK and p38/MAPK, therefore activating several transcription factors, including NF-κB, AP-1 c-jun and c-fos (Ghosh et al , 2010; Lee and Lim, 2011a). In mouse allergic effector cells, DEHP increases AP-1 transcriptional activation via p38 MAPK phosphorylation (Oh and Lim, 2010).…”

Mono-(2-Ethylhexyl) Phthalate Induces Oxidative Stress and Inhibits Growth of Mouse Ovarian Antral Follicles1

“…Elevated ROS levels regulate the expression and activity of these antioxidant enzymes by activating different signaling pathways in different biological systems, which include extracellular signal-regulated kinases (ERKs) and p38 mitogen-activated protein kinases (MAPKs) [66], tyrosine kinase [67], phosphotidylinositol-3-kinase (PI3K)/Akt [68], and protein kinase C [69]. DEHP induces oxidative stress and causes apoptosis in hepatocytes by activating ERK/MAPK and p38/MAPK [70,71]. MEHP activates PI3K/Akt and NF-jB signaling in the testis and induces oxidative stress and germ cell apoptosis [72].…”

Di-(2-ethylhexyl) Phthalate Inhibits Growth of Ovarian Antral Follicles Through an Oxidative Stress Pathway.

“…Recent studies show that DEHP induces oxidative stress via the MAPK-NF-κB pathway ( Lee and Lim, 2011a;Lee and Lim, 2011b) and that NAC decreases the phosphorylation of various kinases (p38 MAPK and ERK) and inhibits the activation of NF-κ (Lee and Lim, 2011b;Sigala et al, 2011). Further, Rojo et al (2004) reported that motifs for NF-κB are located in the promoter regions of SOD.…”

“…Previous studies indicate that both AREs and motifs for NF-κB and AP-1 are present in the promoter regions of most of the antioxidant enzymes, including SOD1, SOD2, CAT and GPX (Banning et al, 2005;Scandalios, 2005). Interestingly, numerous studies have shown that DEHP induces oxidative stress and causes apoptosis in hepatocytes by activating ERK/MAPK and p38/ MAPK, therefore activating several transcription factors, including NF-κB, AP-1 c-jun and c-fos (Ghosh et al, 2010;Lee and Lim, 2011a). In mouse allergic effector cells, DEHP increases AP-1 transcriptional activation via p38 MAPK phosphorylation (Oh and Lim, 2010).…”