Wei Zheng

Nanjing University, Nan-ching, Jiangsu Sheng, China

Are you Wei Zheng?

Claim your profile

Publications (9)40.93 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Triptolide (TP) is a biologically active diterpene triepoxide from the Chinese herb Tripterygium wilfordii Hook f. Here, we identify and explore TAB1 as the binding target of TP in macrophages by using a comprehensive approach combining pull-down assays, in vitro assessments, and pharmaceutical and biological evaluation. We discover that TP inhibits TAK1 kinase activity by interfering with the formation of the TAK1-TAB1 complex, and the binding affinity of TP to TAB1 correlates highly with the inhibitory activity of TP against MAPK pathway activation in macrophages. We also find that the amino acid sequence between positions 373 and 502 of TAB1 is required for TP interaction. Our results suggest that TP could be a selective small-molecule inhibitor of the TAK1-TAB1 complex and that TAB1 could be a potential therapeutic target in inflammatory disease.
    Chemistry & biology 01/2014; · 6.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Post-translational regulation plays a critical role in the control of cell growth and proliferation. The phosphorylation of peroxisome proliferator-activated receptor γ (PPARγ) is the most important post-translational modification. The function of PPARγ phosphorylation has been studied extensively in the past. However, the relationship between phosphorylated PPARγ1 and tumors remains unclear. Here we investigated the role of PPARγ1 phosphorylation in human fibrosarcoma HT1080 cell line. Using the nonphosphorylation (Ser84 to alanine, S84A) and phosphorylation (Ser84 to aspartic acid, S84D) mutant of PPARγ1, the results suggested that phosphorylation attenuated PPARγ1 transcriptional activity. Meanwhile, we demonstrated that phosphorylated PPARγ1 promoted HT1080 cell proliferation and this effect was dependent on the regulation of cell cycle arrest. The mRNA levels of cyclin-dependent kinase inhibitor (CKI) p21(Waf1/Cip1) and p27(Kip1) descended in PPARγ1(S84D) stable HT1080 cell, whereas the expression of p18(INK4C) was not changed. Moreover, compared to the PPARγ1(S84A), PPARγ1(S84D) up-regulated the expression levels of cyclin D1 and cyclin A. Finally, PPARγ1 phosphorylation reduced sensitivity to agonist rosiglitazone and increased resistance to anticancer drug 5-fluorouracil (5-FU) in HT1080 cell. Our findings establish PPARγ1 phosphorylation as a critical event in human fibrosarcoma growth. These findings raise the possibility that chemical compounds that prevent the phosphorylation of PPARγ1 could act as anticancer drugs.
    Experimental Cell Research 01/2014; · 3.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In situ chemical oxidation (ISCO) can be an effective technology for the remediation of soil and groundwater polluted by organic and inorganic contaminants. This study investigated the oxidation of arsenic(III) (As(III)) and diuron using ferrous activated persulfate-based ISCO. The results indicated that Fe(II)/persulfate oxidation could be an effective method to oxidize As(III) and diuron. Effects of pH, S2O8(2-) and Fe(II) amounts on the destruction of As(III) and diuron were examined in batch experiments. Acidic conditions favored the removal of As(III) and diuron. Four chelating agents, citric acid (CA), Na2S2O3, diethylene triamine pentaacetic acid (DTPA) and ethylene diamine tetraacetic acid disodium (EDTA-Na2) were used in attempt to maintain the quantity of ferrous ion in solution. In our experiments, CA and Na2S2O3 were found to be more effective than DTPA and EDTA-Na2. Our results also revealed a widely practical prospect of inorganic chelating agent Na2S2O3. Hydroxyl and sulfate radical were determined to play key roles in the oxidation process by using ethanol and tertiary butanol as molecular probes. Oxidation of As(III) yielded As(V) via the electron-transfer reaction. In the oxidation process of diuron, a stepwise nucleophilic substitution of chlorine by hydroxyl and a stepwise oxidation process of the methyl on the dimethylurea group by hydroxyl and sulfate radical were proposed.
    Journal of hazardous materials 10/2013; · 4.14 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Extracellular signal-regulated kinase (ERK) belongs to the mitogen-activated protein kinases (MAPK) superfamily. Aberrant upregulation and activation of ERK cascades may often lead to tumor cell development. However, how ERK is involved in tumor progression is yet to be defined. In current study, we described that ERK undergoes S-nitrosylation by nitric oxide (NO). ERK S-nitrosylation inhibits its phosphorylation and triggers apoptotic program as verified by massive apoptosis in fluorescence staining. The proapoptotic effect of NO induced S-nitrosylation is reversed by NO scavenger Haemoglobin (HB). Furthermore, an S-nitrosylation dead ERK mutant C183A also demolishes the proapoptotic potential of NO and favors cell survival. Therefore, Cys(183) might be a potential S-nitrosylation site in ERK. In addition, S-nitrosylation is a general phenomenon that regulates ERK activity. These findings identify a novel link between NO-mediated S-nitrosylation and ERK regulation, which provide critical insights into the control of apoptosis and tumor development.
    Scientific Reports 05/2013; 3:1814. · 5.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aim: Malignant melanoma is well known for abundant ROS (reactive oxygen species) that exist in the primary tumor environment. Within this microenvironment, TAMs (tumor-associated macrophages) play substantial roles in multiple steps of tumor development in terms of tumor growth, invasion and metastasis. We therefore aimed to determine whether this high-level ROS in primary melanoma is capable to promote tumor invasiveness by influencing TAM properties. Moreover, we wanted to further investigate probable underlying mechanisms. Results: We characterized malignant melanoma TAMs as heterogeneous phenotype which possesses both M1 and M2 markers. We also revealed a role for high-level intracellular ROS in enhancing pro-invasion signature of TAMs by strongly increasing their TNF-α (tumor necrosis factor α) secretion, which is possibly attributed to ROS-enhanced PPARγ (peroxisome proliferator-activated receptor γ) translocation mediated by MEK-1 (MAPK/ERK kinase 1). Innovation: This is the first study demonstrating that high levels of ROS in primary melanoma environment can influence TAM behaviors. Furthermore, we are also the first to indentify that nucleus-to-cytoplasm translocation of PPARγ is significantly up-regulated by ROS and is responsible for pro-invasiveness capacity of melanoma TAMs. Conclusion: Taken together, our data describe how high level of ROS plays a critical role in enhancing the pro-invasion characteristic of TAMs in malignant melanoma.
    Antioxidants & Redox Signaling 02/2013; · 8.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hepatocarcinoma cancer (HCC), one of the most malignant cancers, occurs significantly more often in men than in women; however little is known about its underlying molecular mechanisms. Here we identify that 17β-estradiol (E2) could suppress tumor growth via regulating the polarization of macrophages. We show that E2 re-administration reduces tumor growth in orthotopic and xenotopic mice HCC models. E2 functions as a suppressor for macrophage alternative activation and tumor progression by keeping estrogen receptor beta (ERβ) away from interacting with ATP synthase-coupling factor 6 (ATP5J), a part ATP synthetase, thus inhibiting JAK1-STAT6 signaling pathway. These studies introduce a novel mechanism for suppressing male-predominant HCC.
    Journal of Biological Chemistry 08/2012; · 4.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A small molecule, 15b-β-hydroxy-5-N-acetylardeemin (IFB07188), was previously isolated from the fungi Aspergillus terreus. However, the toxicological features of this natural product have never been investigated. In present study, we described the anticancer activities of IFB07188. We found that IFB07188 can decrease the viability and invasive potency of multiple cancer cell lines. Further mechanistic investigation demonstrates that cell cycles are arrested at G2/M phase and the arrest is induced by deregulated cell cycle proteins. A concomitant flow cytometric analysis also shows that IFB07188 can trigger massive apoptosis in a dose-dependent manner. The proapoptotic effect of IFB07188-treated cancer cells is characterized by depolarization of mitochondria membrane potential (Δψ(m)) and positive Hochest staining. Finally, results from invasion assay suggest that IFB07188 can suppress tumor cell invasion independent of apoptosis. Collectively, these data establish that IFB07188 can effectively inhibit cancer cell growth and invasiveness, prompting its potential use in cancer chemotherapy.
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 06/2012; 66(7):512-8. · 2.24 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Triptolide, a diterpene triepoxide, is one of the major components of most functional extracts of Tripterygium wilfordii Hook f, which is known to have various biological effects, including immunosuppressive, anti-inflammatory and anti-tumor functions. We studied the inhibitory effect of triptolide on endotoxemia (ETM)-induced oxidative stress, which was induced in C57BL/6 mice by lipopolysaccharide (LPS) and D-galactosamine (D-GalN). Pretreatment with triptolide decreased the reactive oxygen species (ROS) levels, mortality rate and liver injury after LPS/D-GalN injection. We utilized comprehensive proteomics to identify alterations in liver protein expression during pretreatment with triptolide or N-acetylcysteine (NAC) after LPS/D-GalN injection, 44 proteins were found to be related to oxidative stress, mitochondria, metabolism and signal transduction, and 23 proteins of them seemed to be significantly up- or down-regulated. Furthermore, both triptolide and NAC inhibited activation of c-jun NH2-terminal kinases (JNK) and mitogen-activated protein kinase p38 (p38), phosphorylation of inhibitor of nuclear factor-kappa B (IκB) and activation of nuclear factor-κB (NF-κB). These results demonstrated that triptolide inhibited the activation of JNK and p38 by decreasing ROS levels, which in turn inhibited the hepatic injury. In addition, we set and validated the phosphorylation model of extracellular signal-regulated kinase (ERK) and proposed that triptolide probably induced ERK phosphorylation through inhibiting its dephosphorylation rates. These results showed that triptolide can effectively reduce the oxidative stress and partially rescue the damage in the liver induced by LPS/D-GalN.
    Journal of Cellular Biochemistry 11/2011; 113(3):1022-33. · 3.06 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Methylene blue (MB) is a widely studied agent currently under investigation for its properties relating to photodynamic therapy (PDT). Recent studies have demonstrated that MB exhibits profound phototoxicity affecting a variety of tumor cell lines. However, the mechanistic explanation for methylene-blue-mediated photodynamic therapy (MB-PDT) in the context of melanoma therapy is still obscure. In the present study, B16F1 melanoma cells were treated by MB-PDT under different conditions, and thereafter subjected to cell viability detection assays. MB-PDT could induce intense apoptotic cell death through a series of steps beginning with the photochemical generation of reactive oxygen species that activate the caspase-9/caspase-3 apoptosis pathway. Blocking activation of caspase-3 and induction of oxidative stress by caspase inhibitor and by glutathione, respectively, markedly reduced apoptotic cell death in vitro. Importantly, proteomics study defining altered protein expression in treated cells suggests the involvement of several mitochondrial proteins playing important roles in electron transfer chain, implying mitochondrial dysfunction during the treatment. Furthermore, a transplantable mouse melanoma model was utilized to estimate the effectiveness of MB-PDT in vivo. The treated mice displayed decreased tumor size and prolonged survival days, which was associated with enhanced apoptotic cell death. These results, offering solid evidence of the induction of mitochondria-related apoptosis in tumor cells, reveal new aspects of MB-PDT having potential to be a palliative treatment of melanoma.
    Cancer Science 11/2008; 99(10):2019-27. · 3.48 Impact Factor