Zigang Dong

Zhengzhou University, Cheng, Henan Sheng, China

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Publications (287)1641.67 Total impact

  • Yan Li · Xiang Li · Zigang Dong ·
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    ABSTRACT: In this work the ability of EGFR structures to distinguish true inhibitors from decoys in docking and MM-PBSA is assessed by statistical procedures. The docking performance depends critically on the receptor conformation and bound state. The enrichment of known inhibitors is well correlated with the difference between EGFR structures rather than the bound-ligand property. The optimal structures for virtual screening can be selected based purely on the complex information. And the mixed combination of distinct EGFR conformations is recommended for ensemble docking. In MM-PBSA, a variety of EGFR structures have identically good performance in the scoring and ranking of known inhibitors, indicating that the choice of the receptor structure has little effect on the screening.
    Journal of Computer-Aided Molecular Design 10/2015; DOI:10.1007/s10822-015-9877-9 · 2.99 Impact Factor
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    ABSTRACT: The aim of this study was to investigate anti-inflammatory and anti-cancer effects of honokiol (HK) in two oral squamous cancer cell carcinoma (OSCC) cell lines, HN22 and HSC4, through the regulation of inducible nitric oxide synthase (iNOS) and endoplasmic reticulum resident protein 44 (ERp44). Griess assay, zymography, and quantitative PCR were performed to study iNOS expression and subsequent nitric oxide (NO) production in OSCC cell lines. Liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomic analysis was used to elucidate the proteins associated with ER stress and cellular cytotoxic response induced by HK. Pull-down assay and molecular modeling were performed to better understand how HK interacts with ERp44. In vitro and in vivo experiments in which ERp44 expression was knocked down were performed to better understand the effects of ERp44 on a cellular level and anti-cancer effects of HK. Expression levels of iNOS and subsequent NO secretion were reduced in OSCC cell lines treated with HK. ERp44 was significantly decreased in OSCC cell lines by HK treatment. HK directly bound to ERp44, and ERp44 knock-down significantly inhibited oral cancer cell proliferation and colony formation. Moreover, HK treatment effectively inhibited tumor growth and ERp44 levels in BALB/c nude mice bearing HN22 cell xenografts. Our findings suggest that HK inhibited inflammation and induced apoptosis by suppressing both iNOS/NO and ERp44 expression in HN22 and HSC4 cells and xenograft tumors, and thus could be a potent anti-inflammatory and anti-cancer drug candidate for human oral cancer treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Biomaterials 06/2015; 53. DOI:10.1016/j.biomaterials.2015.02.091 · 8.56 Impact Factor
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    ABSTRACT: microRNAs (miRNAs) are involved in the various processes of DNA damage repair and play crucial roles in regulating response of tumors to radiation therapy. Here, we used nasopharyngeal carcinoma (NPC) radio-resistant cell lines as models and found that the expression of miR-504 was significantly up-regulated. In contrast, the expression of nuclear respiratory factor 1 (NRF1) and other mitochondrial metabolism factors, including mitochondrial transcription factor A (TFAM) and oxidative phosphorylation (OXPHOS) complex III were down-regulated in these cell lines. At the same time, the Seahorse cell mitochondrial stress test results indicated that the mitochondrial respiratory capacity was impaired in NPC radio-resistant cell lines and in a miR-504 over-expressing cell line. We also conducted dual luciferase reporter assays and verified that miR-504 could directly target NRF1. Additionally, miR-504 could down-regulate the expression of TFAM and OXPHOS complexes I, III, and IV and impaired the mitochondrial respiratory function of NPC cells. Furthermore, serum from NPC patients showed that miR-504 was up-regulated during different weeks of radiotherapy and correlated with tumor, lymph nodes and metastasis (TNM) stages and total tumor volume. The radio-therapeutic effect at three months after radiotherapy was evaluated. Results indicated that patients with high expression of miR-504 exhibited a relatively lower therapeutic effect ratio of complete response (CR), but a higher ratio of partial response (PR), compared to patients with low expression of miR-504. Taken together, these results demonstrated that miR-504 affected the radio-resistance of NPC by down-regulating the expression of NRF1 and disturbing mitochondrial respiratory function. Thus, miR-504 might become a promising biomarker of NPC radio-resistance and targeting miR-504 might improve tumor radiation response.
    Oncotarget 06/2015; 6(18):15995-6018. DOI:10.18632/oncotarget.4138 · 6.36 Impact Factor
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    ABSTRACT: While cancer incidence and mortality rates in the United States and some European countries have started to decrease, those in developing countries are increasing. China, the most populous developing country, is facing a serious challenge from cancer. Cancer incidence has been increasing for decades, and cancer is the leading cause of death in China. In 2012, the cancer incidence was 174.0 per 100,000 and the cancer mortality was 122.2 per 100,000 in China. In addition to the still-prevalent traditional Chinese cancers of the stomach, liver, esophagus, cervix and nasopharynx, incidence of "Western" cancers such those of the lung, breast and colorectum have increased alarmingly in recent years. These increases are likely due to the lifestyle and environmental changes associated with rapid economic development and population aging. More importantly, a large portion of these cancers are preventable. Researchers in China have made important contributions to cancer prevention research, especially in the traditional Chinese cancers. More cancer prevention research and measures, especially on the major emerging cancers, are urgently needed. This review article highlights some of the past achievements and present needs in cancer prevention research in China, and suggests important areas for future studies. Copyright © 2015, American Association for Cancer Research.
    Cancer Prevention Research 06/2015; 8(8). DOI:10.1158/1940-6207.CAPR-14-0469 · 4.44 Impact Factor
  • Hong‐Gyum Kim · Chengcheng Shi · Ann M. Bode · Zigang Dong ·
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    ABSTRACT: Arsenic exposure has been reported to cause neoplastic transformation through the activation of PcG proteins. In the present study, we show that activation of p38α mitogen-activated protein kinase (MAPK) is required for arsenic-induced neoplastic transformation. Exposure of cells to 0.5 μM arsenic increased CRE and c-Fos promoter activities that were accompanied by increases in p38α MAPK and CREB phosphorylation and expression levels concurrently with AP-1 activation. Introduction of short hairpin (sh) RNA-p38α into BALB/c 3T3 cells markedly suppressed arsenic-induced colony formation compared with wildtype cells. CREB phosphorylation and AP-1 activation were decreased in p38α knockdown cells after arsenic treatment. Arsenic-induced AP-1 activation, measured as c-Fos and CRE promoter activities, and CREB phosphorylation were attenuated by p38 inhibition in BALB/c 3T3 cells. Thus, p38α MAPK activation is required for arsenic-induced neoplastic transformation mediated through CREB phosphorylation and AP-1 activation. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Molecular Carcinogenesis 06/2015; DOI:10.1002/mc.22331 · 4.81 Impact Factor
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    Tae-Gyu Lim · Charles C Lee · Zigang Dong · Ki Won Lee ·
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    ABSTRACT: Ginsenosides are representative pharmaceutical compounds found in various forms in Panax ginseng, a traditional medicinal plant. They are converted to their metabolites Rg2, Rg3, compound K, and others by human intestinal microflora following ingestion. Numerous studies have demonstrated beneficial effects of ginsenosides against aberrant molecular processes responsible for cancer, metabolic diseases and neurodegenerative diseases. Recently, antiaging effects of ginsenosides in human skin have been reported from clinical trial and in vitro model data. Ginsenosides have hence been proposed as promising natural cosmeceutical agents. In this review, we will critically review the known biological effects of several ginsenosides (Rb1, Rg3, Rd and compound K), such as anti-inflammatory and anticancer activities, which arise from the modulation of diverse molecular pathways. The application potential of ginsenosides as cosmeceutical ingredients will also be reviewed.
    Archives for Dermatological Research 05/2015; 307(5). DOI:10.1007/s00403-015-1569-8 · 1.90 Impact Factor
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    ABSTRACT: Recently, biphenolic components derived from the Magnolia family have been studied for anti-cancer, anti-stress, and anti-inflammatory pharmacological effects. However, the pharmacological mechanism of action of 4-O-methylhonokiol (MH) is not clear in oral cancer. The aim of this study was to investigate the role of MH in apoptosis and its molecular mechanism in oral squamous cell carcinoma (OSCC) cell lines, HN22 and HSC4, as well as tumor xenografts. Here, we demonstrated that MH decreased cell growth and induced apoptosis in HN22 and HSC4 cells through the regulation of specificity protein 1 (Sp1). We employed several experimental techniques such as MTS assay, DAPI staining, PI staining, Annexin-V/7-ADD staining, RT-PCR, western blot analysis, immunocytochemistry, immunohistochemistry, TUNEL assay and in vivo xenograft model analysis. MH inhibited Sp1 protein expression and reduced Sp1 protein levels via both proteasome-dependent protein degradation and inhibition of protein synthesis in HN22 and HSC4 cells; MH did not alter Sp1 mRNA levels. We found that MH directly binds Sp1 by Sepharose 4B pull-down assay and molecular modeling. In addition treatment with MH or knocking down Sp1 expression, suppressed oral cancer cell colony formation. Moreover, MH treatment effectively inhibited tumor growth and Sp1 levels in BALB/c nude mice bearing HN22 cell xenografts. These results indicated that MH inhibited cell growth, colony formation and also induced apoptosis via Sp1 suppression in OSCC cells and xenograft tumors. Thus MH is a potent anti-cancer drug candidate for oral cancer. Copyright © 2015. Published by Elsevier Ltd.
    The international journal of biochemistry & cell biology 05/2015; 64. DOI:10.1016/j.biocel.2015.05.007 · 4.05 Impact Factor
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    ABSTRACT: Lung cancer is a leading cause of death worldwide and MET amplification is a major therapeutic limitation in acquired-resistance lung cancer. We hypothesized that butein, a phytochemical, can overcome gefitinib-induced resistance by targeting both EGFR and MET in non-small cell lung cancer (NSCLC). To investigate the ability of butein to target EGFR and MET, we used in silico docking, a library of natural compounds and kinase assays. The effects of butein on growth, induction of apoptosis and expression of EGFR/MET signaling targets were examined in HCC827 (gefitinib-sensitive) and HCC827GR (gefitinib-resistant) NSCLC cells. Results were confirmed in vivo by a HCC827 or HCC827GR cell xenograft mouse model, each treated with vehicle, butein or gefitinib. Butein inhibited phosphorylation and kinase activity of EGFR and MET as well as soft agar colony formation and decreased viability of HCC827 and HCC827GR cells. Butein increased apoptosis-related protein expression in these cells. Results were confirmed by co-treatment with inhibitors of EGFR/MET or double knock-down. Finally, xenograft study results showed that butein strongly suppressed HCC827 and HCC827GR tumor growth. Immunohistochemical data suggest that butein inhibited Ki-67 expression. These results indicate that butein has potent anticancer activity and targets both EGFR and MET in acquired-resistance NSCLC. © 2014 Wiley Periodicals, Inc.
    Molecular Carcinogenesis 04/2015; 54(4). DOI:10.1002/mc.22191 · 4.81 Impact Factor
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    ABSTRACT: Aspirin intake reduces the risk of colorectal cancer (CRC), but the molecular underpinnings remain elusive. Epidermal growth factor receptor (EGFR), which is overexpressed in about 80% of CRC cases, is implicated in the etiology of CRC. Here, we investigated whether aspirin can prevent CRC by normalizing EGFR expression. Immunohistochemistry staining was performed on paraffin-embedded tissue sections from normal colon mucosa, adenomatous polyps from FAP patients who were classified as regular aspirin users or nonusers. The interplay between cyclooxygenase-2 (COX-2) and EGFR was studied in primary intestinal epithelial cells isolated from Apc(Min) mice, immortalized normal human colon epithelial cells (HCEC) as well as murine embryonic fibroblasts (MEFs). Immunohistochemistry staining results established that EGFR overexpression is an early event in colorectal tumorigenesis, which can be greatly attenuated by regular use of aspirin. Importantly, EGFR and COX-2 were co-overexpressed and co-localized with each other in FAP patients. Further mechanistic studies revealed that COX-2 overexpression triggers the activation of the c-Jun-dependent transcription factor, activator protein-1 (AP-1), which binds to the Egfr promoter. Binding facilitates the cellular accumulation of EGFR and lowers the threshold required for pre-neoplastic cells to undergo transformation. Aspirin might exert its chemopreventive activity against CRC, at least partially, by normalizing EGFR expression in gastrointestinal precancerous lesions.
    03/2015; 13(5). DOI:10.1016/j.ebiom.2015.03.019
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    ABSTRACT: Colorectal cancer (CRC) represents the third leading cause of cancer-related death in the United States. Lack of reliable biomarkers remains a critical issue for early detection of CRC. In this study, we investigated the potential predictive values of circulating prostaglandin (PG) biosynthesis in CRC risk. Profiles of circulating PG biosynthesis and platelet counts were determined in healthy subjects (n = 16), familial adenomatous polyposis (FAP) patients who were classified as regular aspirin users (n = 14) or nonusers (n = 24), and CRC patients with (n = 18) or without FAP history (n = 20). Immunohistochemistry staining was performed on biopsy samples. Analysis of circulating PG biosynthesis unexpectedly revealed that CRC progression is accompanied by a pronounced elevation of circulating thromboxane A2 (TXA2) levels. When a circulating TXA2 level of 1000 pg/mL was selected as a practical cutoff point, 95% of CRC patients were successfully identified. Further study suggested that the TXA2 pathway is constitutively activated during colorectal tumorigenesis and required for anchorage-independent growth of colon cancer cells. This study established the importance of the TXA2 pathway in CRC pathophysiology, and laid the groundwork for introducing a TXA2-targeting strategy to CRC prevention, early detection and management.
    02/2015; 2(2):165-171. DOI:10.1016/j.ebiom.2014.12.004
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    Ann M. Bode · Zigang Dong ·
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    ABSTRACT: Cancer is still a major health issue worldwide and identifying novel but safe compounds for prevention and treatment is a high priority. Licorice (Glycyrrhiza) is a perennial plant that is cultivated in many countries and has been reported to exert antioxidant, anti-inflammatory and anticancer effects. However, some components of licorice exert unwanted side effects and therefore identifying safer licorice components would be ideal. The anticancer activities of many of the licorice components appear to include cycle arrest, apoptosis induction, and general antioxidant effects. Commonly reported indirect protein targets important in tumorigenesis include many cell cycle-related proteins, apoptosis-associated proteins, MMP proteins, COX-2, GSK-β, Akt, NF-κB, and MAP kinases. Importantly, several licorice components were reported to directly bind to and inhibit the activities of PI3-K, MKK4, MKK7, JNK1, mTOR, and Cdk2, resulting in decreased carcinogenesis in several cell and mouse models with no obvious toxicity. This review focuses on specific components of licorice for which a direct protein target has been identified.
    02/2015; 1(1):60-71. DOI:10.1007/s40495-014-0015-5
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    ABSTRACT: LMP1, which is encoded by the Epstein-Barr virus, is proposed to be one of the major oncogenic factors involved in nasopharyngeal carcinoma (NPC). Previous studies demonstrated that down-regulation of LMP1 by LMP1-targeted DNAzyme (DZ1) increases the radiosensitivity of NPC. However, the mechanism by which DZ1 contributes to this radiosensitivity remains unclear. In this study, we determined whether a DZ1 blockade of LMP1 expression has an overall positive effect on the radiotherapy of NPCs by repressing HIF-1/VEGF activity and to investigate the mechanisms underlying LMP1-induced HIF-1 activation in NPC cells. The results showed that DZ1 inhibited the microtubule-forming ability of HUVECs co-cultured with NPC cells, which occurs with the down-regulation of VEGF expression and secretion. Moreover, LMP1 increases phosphorylated JNKs/c-Jun signaling, which is involved in the regulation of HIF-1/VEGF activity. After silencing LMP1 and decreasing phosphorylation of JNKs, NPC cells exhibited an enhanced radiosensitivity. Furthermore, in vivo experiments revealed a significant inhibition of tumor growth and a marked reduction of the Ktrans parameter, which reflects the condition of tumor micro-vascular permeability. Taken together, our data suggested that VEGF expression is increased by LMP1 through the JNKs/c-Jun signaling pathway and indicated that DZ1 enhances the radiosensitivity of NPC cells by inhibiting HIF-1/VEGF activity.
    Oncotarget 01/2015; 6(8). DOI:10.18632/oncotarget.3331 · 6.36 Impact Factor
  • Ann M. Bode · Zigang Dong ·
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    ABSTRACT: Even though the health benefits and risks of coffee consumption have been debated for decades, epidemiological and animal studies are contradictory. Coffee includes a complex mixture of compounds, including various highly active phenols. Carcinogenesis is a complicated process involving hundreds of genes and gene products that regulate innumerable cellular functions. An emerging opinion is that cancer might be prevented with small molecules that target specific or multiple cancer genes or signaling proteins. Promising small molecule inhibitors include dietary factors-hence the interest in coffee and its role in chemoprevention. However, developing dietary factors or phytochemicals as anticancer agents is based on discovering specific molecular targets. We have shown that phytochemicals with defined mechanisms of action based on molecular target identification can be linked to successful drug discovery. This review chapter focuses on the anticancer effects and molecular targets of coffee, especially the caffeoylquinic acids and their phenolic degradation products.
    Coffee in Health and Disease Prevention, 01/2015: pages 673-680; , ISBN: 9780124095175
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    ABSTRACT: Necroptosis/regulated necrosis is a caspase-independent, but receptor interacting protein kinase (RIPK)-dependent form of cell death. In previous studies, neoalbaconol (NA), a constituent extracted from Albatrellus confluens, was demonstrated to induce necroptosis in some cancer cell lines. The molecular mechanism of NA-induced necroptosis is described in this research study. We determined that NA-induced cell death is partly dependent on tumor necrosis factor α (TNFα) feed-forward signaling. More importantly, NA abolished the ubiquitination of RIPK1 by down-regulating E3 ubiquitin ligases, cellular inhibitors of apoptosis protein 1/2 (cIAP1/2) and TNFα receptor-associated factors (TRAFs). The suppression of RIPK1 ubiquitination induced the activation of the non-canonical nuclear factor-κB (NF-κB) pathway and stimulated the transcription of TNFα. Moreover, we also found that NA caused RIPK3-mediated reactive oxygen species (ROS) production and contribution to cell death. Taken together, these results suggested that two distinct mechanisms are involved in NA-induced necroptosis and include RIPK1/NF-κB-dependent expression of TNFα and RIPK3-dependent generation of ROS.
    Oncotarget 12/2014; 6(4). DOI:10.18632/oncotarget.3038 · 6.36 Impact Factor
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    ABSTRACT: Non-small-cell lung cancer (NSCLC) is associated with diverse genetic alterations including mutation of epidermal growth factor receptor (EGFR). Isoliquiritigenin (ILQ), a chalcone derivative, possesses anticancer activities. In the present study, we investigated the effects of ILQ on the growth of tyrosine kinase inhibitor (TKI)-sensitive and -resistant NSCLC cells and elucidated its underlying mechanisms. Treatment with ILQ inhibited growth and induced apoptosis in both TKI-sensitive and -resistant NSCLC cells. ILQ-induced apoptosis was associated with the cleavage of caspase-3 and poly-(ADP ribose)-polymerase, increased expression of Bim and reduced expression of Bcl-2. In vitro kinase assay results revealed that ILQ inhibited the catalytic activity of both wildtype and double mutant (L858R/T790M) EGFR. Treatment with ILQ inhibited the anchorage-independent growth of NIH3T3 cells stably transfected with either wildtype or double-mutant EGFR with or without EGF stimulation. ILQ also reduced the phosphorylation of Akt and ERK1/2 in both TKI-sensitive and -resistant NSCLC cells, and attenuated the kinase activity of Akt1 and ERK2 in vitro. ILQ directly interacted with both wildtype and double-mutant EGFR in an ATP-competitive manner. A docking model study showed that ILQ formed two hydrogen bonds (Glu762 and Met793) with wildtype EGFR and three hydrogen bonds (Lys745, Met793 and Asp855) with mutant EGFR. ILQ attenuated the xenograft tumor growth of H1975 cells, which was associated with decreased expression of Ki-67 and diminished phosphorylation of Akt and ERK1/2. Taken together, ILQ suppresses NSCLC cell growth by directly targeting wildtype or mutant EGFR.
    Journal of Biological Chemistry 11/2014; 289(52). DOI:10.1074/jbc.M114.585513 · 4.57 Impact Factor
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    ABSTRACT: Soy isoflavone is an attractive source of functional cosmetic materials with anti-wrinkle, whitening and skin hydration effects. After consumption, the majority of soy isoflavones are converted to their metabolites in the human gastrointestinal tract. To understand the physiological impact of soy isoflavone on the human body, it is necessary to evaluate and address the biological function of its metabolites. In this study, we investigated the effect of 6,7,4'-trihydroxyisoflavone (6,7,4'-THIF), a major metabolite of daidzein, against solar UV (sUV)-induced matrix metalloproteinases (MMPs) in normal human dermal fibroblasts. MMPs play a critical role in the degradation of collagen in skin, thereby accelerating the aging process of skin. The mitogen-activated protein/extracellular signal-regulated kinase (MEK)/extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MKK)3/6/p38 and MKK4/c-Jun N-terminal kinases (JNK) signaling pathways are known to modulate MMP-1 function, and their activation by sUV was significantly reduced by 6,7,4'-THIF pretreatment. Our results also indicated that the enzyme activity of protein kinase C (PKC)α, an upstream regulator of MKKs signaling, is suppressed by 6,7,4'-THIF using the in vitro kinase assay. Furthermore, the direct interaction between 6,7,4'-THIF and endogenous PKCα was confirmed using the pull-down assay. Not only sUV-induced MMP-1 expression, but also sUV-induced signaling pathway activation were decreased in PKCα knockdown cells. Overall, we elucidated the inhibitory effect of 6,7,4'-THIF on sUV-induced MMPs and suggest PKCα as its direct molecular target.
    International Journal of Molecular Sciences 11/2014; 15(11):21419-32. DOI:10.3390/ijms151121419 · 2.86 Impact Factor
  • Ann M Bode · Zigang Dong ·
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    ABSTRACT: Consuming plants for their presumed health benefits has occurred since early civilizations. Phytochemicals are found in various plants that are frequently included in the human diet and are generally thought to be safe for consumption because they are produced naturally. However, this is not always the case and in fact many natural compounds found in several commonly consumed plants are potential carcinogens or tumor promoters and should be avoided.
    Cancer Prevention Research 10/2014; 8(1). DOI:10.1158/1940-6207.CAPR-14-0160 · 4.44 Impact Factor
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    ABSTRACT: Various health effects have been attributed to the ginsenoside metabolite 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol (GPD); however, its effect on ultraviolet (UV)-induced matrix metalloproteinase (MMP)-1 expression and the mechanism underlying this effect are unknown. We examined the inhibitory effect of GPD on UV-induced MMP-1 expression and its mechanisms in human dermal fibroblasts (HDFs). GPD attenuated UV-induced MMP-1 expression in HDFs and suppressed the UV-induced phosphorylation of mammalian target of rapamycin (mTOR) and p70S6K without inhibiting the activity of phosphatidylinositol 3-kinase and Akt, which are well-known upstream kinases of mTOR. GPD augmented the phosphorylation of liver kinase B1 (LKB1) and adenosine monophosphate-activated protein kinase (AMPK), which are inhibitors of mTOR, to a greater extent than UV treatment alone. Similar to GPD, 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranosyl 5′-monophosphate (AICAR), an activator of AMPK, augmented UV-induced AMPK phosphorylation to a greater extent than UV treatment alone, resulting in the inhibition of MMP-1 expression. AICAR also decreased the phosphorylation of mTOR and p70S6K. However, compound C, an antagonist of AMPK, increased MMP-1 expression. In HDF cells with AMPK knock-down using shRNA, MMP-1 expression was increased. These results indicate that AMPK activation plays a key role in MMP-1 suppression. Additionally, the cAMP-dependent protein kinase (PKA) inhibitor, H-89, antagonized GPD-mediated MMP-1 suppression via the inhibition of LKB1. Our results suggest that the suppressive activity of GPD on UV-induced MMP-1 expression is due to the activation of AMPK as a downstream of the PKA-LKB1 pathway. J. Cell. Biochem. © 2014 Wiley Periodicals, Inc.
    Journal of Cellular Biochemistry 10/2014; 115(10). DOI:10.1002/jcb.24833 · 3.26 Impact Factor
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    ABSTRACT: 9-cis-UAB30 (UAB30) and Targretin are well-known retinoid X receptor (RXR) agonists. They were highly effective in decreasing the incidence of methylnitrosourea (MNU)-induced mammary cancers. However, whether the anti-mammary cancer effects of UAB30 or Targretin originate from the activation of RXR is unclear. In the present study, we hypothesized that UAB30 and Targretin not only affect RXR, but likely influence one or more off-target proteins. Virtual screening results suggest that Src is a potential target for UAB30 and Targretin that regulates extracellular matrix (ECM) molecules and cell motility and invasiveness. In vitro kinase assay data revealed that UAB30 or Targretin interacted with Src and attenuated its kinase activity. We found that UAB30 or Targretin substantially inhibited invasiveness and migration of MCF-7 and SK-BR-3 human breast cancer cells. We examined the effects of UAB30 and Targretin on the expression of matrix metalloproteinases (MMP)-9, which are known to play an essential role in tumor invasion. We show that activity and expression of MMP-9 were decreased by UAB30 or Targretin. Western blot data showed that UAB30 or Targretin decreased AKT and its substrate molecule p70s6k, which are downstream of Src in MCF-7 and SK-BR-3 cells. Moreover, knocking down the expression of Src effectively reduced the sensitivity of SK-BR-3 cells to the inhibitory effects of UAB30 and Targretin on invasiveness. Taken together, our results demonstrate that UAB30 and Targretin each inhibit invasion and migration by targeting Src in human breast cancer cells. © 2014 Wiley Periodicals, Inc.
    Molecular Carcinogenesis 10/2014; 54(12). DOI:10.1002/mc.22232 · 4.81 Impact Factor
  • Cong Peng · Wei Li · Xiang Chen · Zigang Dong ·

    Cancer Research 10/2014; 74(19 Supplement):4440-4440. DOI:10.1158/1538-7445.AM2014-4440 · 9.33 Impact Factor

Publication Stats

9k Citations
1,641.67 Total Impact Points


  • 2015
    • Zhengzhou University
      Cheng, Henan Sheng, China
  • 1997-2015
    • University of Minnesota Duluth
      • • Department of Chemistry and Biochemistry
      • • College of Pharmacy
      Duluth, Minnesota, United States
  • 2013
    • The Advanced Institutes of Convergence Technology
      Yeoncheon Gun, South Korea
  • 2010-2013
    • Seoul National University
      • • Department of Molecular Medicine and Biopharmaceutical Sciences (WCU)
      • • Department of Agricultural Biotechnology
      Sŏul, Seoul, South Korea
  • 2011
    • Catholic University of Korea
      Sŏul, Seoul, South Korea
  • 2009
    • Molecular and Cellular Biology Program
      • Department of Molecular and Cellular Biology
      Seattle, Washington, United States
  • 2008
    • Chosun University
      • College of Pharmacy
      Gwangju, Gwangju, South Korea
  • 2006
    • Pacific Institute of Bioorganic Chemistry
      Wladiwostok, Primorskiy, Russia
  • 2005
    • Johns Hopkins University
      • Division of Pulmonary and Critical Care Medicine
      Baltimore, Maryland, United States
    • Hunan University
      Ch’ang-sha-shih, Hunan, China