Yan-Na Cheng

University of Jinan (Jinan, China), Chi-nan-shih, Shandong Sheng, China

Are you Yan-Na Cheng?

Claim your profile

Publications (22)62.19 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Riccardin D-26, a synthesized macrocyclic bisbibenzyl compound, might possess anti-cancer properties. We aimed to evaluate the efficacy of Riccardin D-26 as a candidate compound for treatment of cancers with sensitive or drug resistant cells. METHODS: Experiments were performed on human oral squamous carcinoma cells KB and vincrinstin-selected MDR cells KB/VCR. The inhibition of cell growth was evaluated by colorimetric and clonogenic assays. The apoptotic cells were determined by the Annexin V-FITC/PI staining assay. JC-1 fluorescence probe was used to examine the mitochondria membrane potential (MMP). Further experiment was performed in nude mice bearing KB or KB/VCR xenografts. Riccardin D-26 was administered by injection for 2weeks. The specimens of KB and KB/VCR xenografts were removed for TUNEL staining and Western blotting analysis. RESULTS: Riccardin D-26 significantly inhibited cancer growth in both KB and KB/VCR cells. Riccardin D-26's activity in cancer cells was greater than that in human normal liver cells. In mice, Riccardin D-26 effectively prevented the growth of KB and KB/VCR xenografts without significant toxicity. Further studies suggested that Riccardin D-26 inhibited cancer growth through inducing apoptosis in activation of mitochondria-mediated intrinsic apoptosis pathway. Riccardin D-26 also possessed the activity in regulation of mitogen-related protein kinases such as MAPK and PI3K/Akt, which is associated with its inhibitory effect on KB/VCR cells. CONCLUSIONS: Riccardin D-26 possessed the activity against both sensitive KB and MDR KB/VCR cancer cells. GENERAL SIGNIFICANCE: Riccardin D-26 could be a promising agent for treatment of cancers with sensitive or drug resistant cells.
    Biochimica et Biophysica Acta 10/2012; · 4.66 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: PTEN (Phosphatase and tensin homolog deleted on chromosome 10) is a tumor suppressor and has been suggested recently to be involved in the regulation of cardiovascular diseases. The molecular mechanisms of this regulation are however poorly understood. This study shows that down regulation of PTEN expression and activity by angiotensin II (Ang II) increased proliferation and migration of vascular smooth muscle cells (VSMCs). The presence of Ang II induced rapid PTEN phosphorylation and oxidation in accordance with increased AKT and FAK phosphorylation. The Ang II-mediated VSMC proliferation and migration was inhibited when cellular PTEN expression was increased by AT1 inhibitor losartan, PPARγ agonist rosiglitazone, NF-κB inhibitor BAY 11-7082. Over expression of PTEN in VSMCs by adenovirus transduction also resulted in inhibition of cell proliferation and migration in response to Ang II. These results suggest that PTEN down-regulation is involved in proliferation and migration of VSMCs induced by Ang □. This provides insight into the molecular regulation of PTEN in vascular smooth muscle cells and suggests that targeting the action of PTEN may represent an effective therapeutic approach for the treatment of cardiovascular diseases. J. Cell. Biochem. © 2012 Wiley Periodicals, Inc.
    Journal of Cellular Biochemistry 08/2012; · 3.06 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Previously, we reported that retigeric acid B (RB), a natural pentacyclic triterpenic acid isolated from lichen, inhibited cell growth and induced apoptosis in androgen-independent prostate cancer (PCa) cells. However, the mechanism of action of RB remains unclear. In this study, we found that using PC3 and DU145 cells as models, RB inhibited phosphorylation levels of IκBα and p65 subunit of NF-κB in a time- and dosage-dependent manner. Detailed study revealed that RB blocked the nuclear translocation of p65 and its DNA binding activity, which correlated with suppression of NF-κB-regulated proteins including Bcl-2, Bcl-x(L), cyclin D1 and survivin. NF-κB reporter assay suggested that RB was able to inhibit both constitutive activated-NF-κB and LPS (lipopolysaccharide)-induced activation of NF-κB. Overexpression of RelA/p65 rescued RB-induced cell death, while knockdown of RelA/p65 significantly promoted RB-mediated inhibitory effect on cell proliferation, suggesting the crucial involvement of NF-κB pathway in this event. We further analyzed antitumor activity of RB in in vivo study. In C57BL/6 mice carrying RM-1 homografts, RB inhibited tumor growth and triggered apoptosis mainly through suppressing NF-κB activity in tumor tissues. Additionally, DNA microarray data revealed global changes in the gene expression associated with cell proliferation, apoptosis, invasion and metastasis in response to RB treatment. Therefore, our findings suggested that RB exerted its anti-tumor effect by targeting the NF-κB pathway in PCa cells, and this could be a general mechanism for the anti-tumor effect of RB in other types of cancers as well.
    PLoS ONE 01/2012; 7(5):e38000. · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A112 is a tamibarotene dimethylaminoethyl ester considered a candidate compound for the treatment of acute promyelocytic leukemia (APL) and acute myeloid leukemia (AML). Our goal in this study was to evaluate the efficacy of anti-cancer activity, beginning by studying its inhibitory effects on leukemia cells and then comparing it to tamibarotene. A112 effectively inhibited the growth of HL-60 and NB4 cells as estimated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The inhibitory effect of A112 was confirmed in mice in which A112 delayed the growth of HL-60 xenografts after 3 weeks' injection. The efficacy of A112 on leukemia cell growth was stronger than that of tamibarotene at the same dosage. The detection of A112 and tamibarotene in plasma of rats showed that A112 might sustain release of its hydrolysate tamibarotene, and the concentration was maintained at a higher level and for a longer time than that of tamibarotene injection. We studied the differentiation morphologies of leukemic cells exposed to A112 or tamibarotene. The number of differentiated NB4 cells was increased, suggesting that A112 possessed differentiation activity in the inhibition of leukemia growth. Further studies showed that the expression of CD11b, a marker of terminal granulocyte differentiation, was increased as estimated by flow cytometry with a direct immunofluorescence assay. A112 was found to induce the activation of CCAAT/enhancer-binding protein β (C/EBPβ) and cyclin-dependent kinase (CDK) inhibitors p21(Waf1/cip1) and p27(Kip1) while cell growth was inhibited. These activities of A112 were greater than those of tamibarotene. The higher efficacy of A112 was also evidenced by induction of apoptosis in leukemia cells. A112 induced a greater number of annexin V-positive cells than did tamibarotene as measured by flow cytometry analysis. Treatment of mice with A112 resulted in stronger terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining in HL-60 xenografts. Western blot analysis revealed that A112 increased the expression of caspase-3, caspase-9 and cleaved poly(ADP-ribose) polymerase (PARP) in leukemia cells both in vitro and in vivo, indicating that induction of apoptosis was involved in the inhibition of leukemia growth. Taken together, these results suggest that A112 is a highly effective derivative of trans retinoic acid and a potential candidate compound for the treatment of leukemia.
    Leukemia & lymphoma 08/2011; 53(2):295-304. · 2.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: LYP is a bestatin dimethylaminoethyl ester which inhibits aminopeptidase N (APN/CD13). Our goal in this study was to evaluate LYP as a candidate compound for cancer treatment, beginning by studying its inhibitory effects on tumors and then comparing it to bestatin. Experiments were performed on human ovarian carcinoma (OVCA) ES-2 and SKOV-3 cell lines, which have high and low levels of APN/CD13 respectively. LYP effectively inhibited ES-2 cell growth as estimated by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and the trypan blue dye-exclusion test. LYP significantly suppressed APN/CD13 activity on the surface of ES-2 cells as measured by quantifying the enzymatic cleavage of the substrate L-leucine-p-nitroanilide. The inhibitory effects of LYP were greater than those of bestatin at the same concentrations. In contrast, LYP was a weak inhibitor of SKOV-3 cell growth, suggesting that LYP may inhibit ES-2 cell growth via suppression of APN/CD13. Inhibition of APN/CD13 expression was also demonstrated with immunofluorescent flow cytometry and Western blot analysis. Inhibitory effects of LYP were confirmed by using a mouse model in which LYP delayed the growth of ES-2 xenografts in mice after 2 weeks of LYP injections. Inhibition of APN/CD13 expression was demonstrated in the ES-2 xenografts using Western blot analysis. The inhibitory effects of LYP on the ES-2 xenografts were stronger than those of bestatin. These results suggest that LYP has a powerful inhibitory effect on the growth of OVCA cells and that the mechanism may be via a decrease in the expression of APN/CD13.
    Investigational New Drugs 08/2011; 29(4):574-82. · 3.50 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Riccardin D is a novel macrocyclic bisbibenzyl compound extracted from Chinese liverwort plant Dumortiera hirsuta. Our previous studies showed that riccardin D is a DNA topo II inhibitor and has therapeutic potential for treatment of cancers. In this combined in vitro and in vivo study, we examined the inhibitory effects of riccardin D on tumor angiogenesis and the subsequent effect of anticancer activity was evaluated. Incubation with riccardin D weakly inhibited the proliferation of human umbilical vascular endothelial cells (HUVEC) as estimated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The scratch wound experiment showed that riccardin D effectively decreased the motility and migration of HUVEC cells. Riccardin D inhibited the formation of capillary tube as demonstrated by decrease of branch points formed by HUVEC cells on 3-D Matrigel. We examined the levels of angiogenic factors including vascular endothelial growth factor (VEGF), VEGF receptor 2, epidermal growth factor receptor (EGF receptor), and matrix metalloproteinase (MMPs) in HUVEC cells. The expressions of VEGF, phospho-VEGF receptor 2, EGF receptor and MMP-2 were significantly reduced by riccardin D as estimated by Western blot assay and real-time quantitative PCR analysis. The decrease of VEGF was also detected in riccardin D-treated human lung cancer H460 cells. The anticancer activity of riccardin D was then evaluated in a mouse model in which riccardin D delayed the growth of H460 xenografts without obvious toxicity to animals after three weeks injection. To evaluate the role of antiangiogenesis of riccardin D in mice, CD34 immunohistochemical staining was employed to analyze the mean vascular density in H460 xenograft tissues. The number of blood vessels was significantly decreased after riccardin D treatment. These results suggest that riccardin D display the inhibitory effect on growth of human lung carcinoma cells and that the inhibition of angiogenesis may involve in anticancer activity of riccardin D.
    European journal of pharmacology 06/2011; 667(1-3):136-43. · 2.59 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Our previous study revealed that LYP, a bestatin dimethylaminoethyl ester, inhibited the growth of human ovarian carcinoma ES-2 xenografts in mice and suppressed aminopeptidase N (APN/CD13) activity more potently than bestatin. In this study, we examined the inhibitory effect of LYP on migration and formation of capillary tube of human umbilical vascular endothelial cells (HUVECs) in vitro and anti-angiogenesis in ES-2 xenografts in mice. LYP did not possess cytotoxicity to HUVEC proliferation according to the MTT assay and trypan blue exclusion assay. However, APN/CD13 activity on cell surface of HUVECs was suppressed in the presence of LYP as measured by quantifying the enzymatic cleavage of the substrate l-leucine-p-nitroanilide. The assays of scratch and transwell chamber showed that LYP significantly inhibited HUVEC migration and invasion through Matrigel coated polycarbonate filters. Capillary tube formation assay revealed that the number of branch points formed by HUVECs on 3-D Matrigel was reduced after incubation with LYP. The anti-angiogenesis of LYP was verified in ES-2 xenografts in mice. The mean vascular density (MVD) and mean vascular luminal diameter (MVLD) were markedly reduced by LYP after two weeks of intravenous injection as evaluated by CD34 immunohistochemical staining. LYP suppression of cancer angiogenesis was greater than that of bestatin. The inhibition of angiogenic molecules may involve in anti-angiogenesis of LYP. The levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and transforming growth factor-alpha (TGF-α) were decreased in HUVECs and ES-2 xenografts after treatment with LYP as determined by Western blot analysis. These results indicated that the high efficacy of LYP may partially relate to the inhibition of angiogenesis.
    Microvascular Research 06/2011; 82(2):122-30. · 2.93 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Multidrug resistance (MDR) of tumor cells is a major obstacle in chemotherapeutic cancer treatment. Over-expression of glutathione S-transferase π (GSTπ) is one of the mechanisms contributing to MDR. In this study, we investigated the reversal of MDR by DLJ14, a ligustrazine derivate, in adriamycin (Adr) resistant human myelogenous leukemia (K562/A02) cells by modulating the expression of GSTπ and the activity of GST-related enzymes. In the MTT test, DLJ14 showed a weak inhibition on proliferation of both K562/A02 and K562 cells, while verapamil at the same concentration showed a much stronger inhibition. The sensitivity of K562/A02 cells to cytotoxic killing by Adr was enhanced by incubation with DLJ14 as a result of the increased intracellular accumulation of Adr. The accumulation of Adr induced by DLJ14 may due to down regulation of GST-related enzyme activity. Western blot analysis and RT-PCR showed that DLJ14 was able to inhibit the protein expression and mRNA expression of GSTπ in K562/A02 cells. Moreover, DLJ14 increased the expression of cellular c-Jun NH(2)-terminal kinase (JNK) in K562/A02 cells exposure to Adr. This is consistent with the inhibition of GSTπ. These results demonstrate that DLJ14 may be an attractive new agent for the chemosensitization of cancer cells.
    Toxicology in Vitro 03/2011; 25(4):937-43. · 2.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: (2S,4R)-methyl 1-acetyl-4-(N-(4-bromophenyl)sulfamoyloxy)pyrrolidine-2-carboxylate (CIP-A5) is the N1-acetyl substituted pyrrolidine derivative which was designed against the structure of matrix metalloproteinase (MMP-2) and MMP-9. CIP-A5 has been considered as a candidate compound for treatment of liver cirrhosis. In this study, we evaluated the efficacy of CIP-A5 on the activity of hepatic stellate cells. CIP-A5 prevented the transforming growth factor β (TGF-β)-induced proliferation of hepatic stellate HSC-T6 cells as estimated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. CIP-A5 stimulated MMPs activity as evidenced by an increase of degradation of succinylated gelatin. Gelatin zymography analysis showed that CIP-A5 stimulated the secretion and activity of MMP-2 and MMP-9 in HSC-T6 cells. This stimulatory effect on MMPs was verified by the observation of increased expression of MMP-2 and MMP-9 as evaluated by Western blot assay. At the same time, a significant decrease of the expression of tissue inhibitors of matrix metalloproteinases-1 (TIMP-1) was observed, suggesting a modulation of the balance of MMPs/TIMPs in hepatic stellate cells. CIP-A5 treatment also resulted in suppression of the profibrogenic cytokines, such as TGF-β, tumor necrosis factor alpha (TNF-α) and connective tissue growth factor (CTGF) in HSC-T6 cells. CIP-A5 did not have cytotoxicity to human normal hepatic cells. These results implied that CIP-A5 could selectively ameliorate the process of liver cirrhosis through modulation of activated hepatic stellate cell activity, which offers hope for prevention and treatment of this devastating end-stage liver disease.
    Toxicology in Vitro 02/2011; 25(4):897-904. · 2.65 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We studied the effect of riccardin D, a macrocyclic bisbibenzyl, which was isolated from the Chinese liverwort plant, on human leukemia cells and the underlying molecular mechanism. Riccardin D had a significant antiproliferative effect on human leukemia cell lines HL-60, K562 and its multidrug resistant (MDR) counterpart K562/A02 cells, but showed no effect on the topoisomerase-II-deficient HL-60/MX2 cells, as measured by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The pBR322 DNA relaxation assay revealed that riccardin D selectively inhibited the activity of topoisomerase II (topo II). The suppression of topo II activity by riccardin D was stronger than that of etoposide, a known topo II inhibitor. After treatment with riccardin D, nuclear extracts of leukemia K562 and K562/A02 cells left the majority of pBR322 DNA in a supercoiled form. Further examination showed that riccardin D effectively induced HL-60, K562 and K562/A02 apoptosis as evidenced by externalization of phosphatidylserine and formation of DNA ladder fragments. The activation of cytochrome c, caspase-9, caspase-3 and cleaved poly ADP-ribose polymerase (PARP) was also enhanced, as estimated by Western blot analysis. By contrast, riccardin D was unable to induce apoptosis in the topoisomerase-II-deficient HL-60/MX2 cells, indicating that the induction of apoptosis by riccardin D was due to the inhibition of topo II activity. In addition, riccardin D was able to significantly decrease P-glycoprotein (P-gp) expression in K562/A02 cells. Taken together, our data demonstrate that riccardin D is a novel DNA topo II inhibitor which can induce apoptosis of human leukemia cells and that it has therapeutic potential for both regular and MDR strains of leukemia cells.
    Investigational New Drugs 10/2010; 30(1):212-22. · 3.50 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A novel ligustrazine derivative, tetramethylpyrazine diphenylmethyl piperazidine (TMPDP), prepared by hybridization and bioisosteric replacement of the molecular structure of TMP, was studied for its protective effects on oxidative damage of human umbilical vein endothelial cells (HUVECs) in response to hydrogen peroxide (H2O2). The antioxidative effect of TMPDP was assessed by the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) test. Cell viability was measured using a 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The activity of lactate dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione peroxidase (GSH) and the content of malondialdehyde (MDA) in cells were determined by commercial kits. The intracellular formation of reactive oxygen species (ROS) and the concentration of free intracellular calcium ([Ca2+]i) were determined using DCFH-DA assay and with fura-2/AM fluorimetry, respectively. Results showed that TMPDP had a moderate antioxidative effect against DPPH. Cell viability was decreased markedly by exposure to H2O2. Introduction of TMPDP, however, significantly increased cell viability, markedly reduced LDH release from cells and decreased lipid peroxidation in response to H2O2 treatment. These effects of TMPDP were accompanied by increased activity of the endogenous antioxidant enzymes, SOD and GSH, reduced production of ROS and reduced intracellular concentration of Ca2+. These results suggest that TMPDP protects HUVECs against oxidative damage by scavenging ROS and regulates intracellular calcium concentration. This might have important implications for the development of new agents for the effective treatment of vascular disease.
    Pharmazie 10/2010; 65(10):755-9. · 0.96 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: QA3 is a derivative of the substituted 1,3-dimethyl-1H-quinoxalin-2-ones, which are compounds that may selectively antagonize P-glycoprotein (P-gp) in multidrug resistance (MDR) cancer cells. Our previous work identified QA3 as a candidate compound for reversing MDR in cancer cells. In the present study, we found that QA3 significantly decreases the intracellular level of ATP, stimulates ATPase activity in membrane microsomes and decreases protein kinase C (PKC) activity. These results indicated that QA3 inhibits P-gp activity by blocking ATP hydrolysis and ATP regeneration. Furthermore, QA3 triggered and increased adriamycin-induced K562/A02 cell apoptosis as evidenced by Annexin V-FITC plus PI staining.Western blot analysis showed that the levels of cleaved caspase-9 and cleaved caspase-3 proteins increased, and similarly, the levels of procaspase-9 and procaspase-3 decreased after QA3 treatment. Consequently, poly ADP-ribose polymerase (PARP) activity increased as evidenced by the presence of the PARP cleavage product in K562/A02 cells. QA3 also enhanced the potency of adriamycin against K562/A02 cells as demonstrated by increased apoptosis and activation of caspase-9,-3 and PARP. These data support the observation that P-gp activity is inhibited after QA3 treatment. Moreover, these results indicate that QA3 is a novel MDR reversal agent with potent inhibitory action against P-gp MDR cancer cells.
    Pharmacological reports: PR 03/2010; 62(2):333-42. · 1.97 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A tetramethylpyrazine analogue, CXC195, was synthesized by the Boekelheide reaction, in which the second methyl group of tetramethylpyrazine (TMP) was replaced with (4,4'-fluorine) diphenyl-methyl-1-piperazidine, the active group of flunarizine. We have observed protective effects of CXC195 on vascular endothelial cell survival under oxidative stress in previous study. The aim of the present study was to investigate the effects of CXC195 against apoptosis induced by hydrogen peroxide in human umbilical vein endothelial cells (HUVECs). Accordingly, a biochemical approach to elucidate the apoptotic signal pathways was attempted. HUVECs were exposed to 150 muM H(2)O(2) for 12 h, resulting in an increase of apoptotic cells assessed by the nuclear staining assay and flow cytometry. Mitochondrial membrane potential was detected by retention of rhodamine123. The concentration of free intracellular calcium was determined by fura-2/AM fluorometry. Co-incubation with CXC195 reduced the percentage of apoptotic cells and inhibited the loss of mitochondrial membrane potential and intracellular calcium overload induced by H(2)O(2). Induction of p53, the activation of caspase-3 by H(2)O(2) which accompanying downregulation of bcl-2, was blocked by CXC195. In addition, CXC195 clearly improved phosphorylation levels of the antiapoptotic extracellular signal-regulated kinase-1/2 (ERK1/2) in cells undergoing oxidative damage. Moreover, CXC195 showed stronger effects on inhibition of apoptotic cells and loss of mitochondrial membrane potential and activation of phosphorylated ERK1/2 than TMP. These results suggest that CXC195 prevents reactive oxygen species-induced apoptosis through inhibition of the mitochondria-dependent caspase-3 pathway and ERK pathway to show a better beneficial effect in protecting endothelial cells than TMP.
    Biological & Pharmaceutical Bulletin 01/2010; 33(3):432-8. · 1.85 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Salvia plebeia R. Br is a traditional Chinese herb which has been considered as an inflammatory mediator used for treatment of many infectious diseases including hepatitis. Previously, the compound homoplantaginin was isolated in our group. Hence, we evaluated the protective effects of homoplantaginin on hepatocyte injury. Homoplantaginin displayed an antioxidant property in a cell-free system and showed IC(50) of reduction level of DPPH radical at 0.35 microg/ml. In human hepatocyte HL-7702 cells exposed to H(2)O(2), the addition of 0.1-100 microg/ml of homoplantaginin, which did not have a toxic effect on cell viability, significantly reduced lactate dehydrogenase (LDH) leakage, and increased glutathione (GSH), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) in supernatant. In vivo assay, we employed the model of Bacillus Calmette-Guérin (BCG)/lipopolysaccharide (LPS)-induced hepatic injury mice to evaluate efficacy of homoplantaginin. Homoplantaginin (25-100mg/kg) significantly reduced the increase in serum alanine aminotranseferase (ALT) and aspartate aminotransferase (AST), decreased the levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1). The same treatment also reduced the content of thiobarbituric acid-reactive substances (TBARS), elevated the levels of GSH, GSH-Px and SOD in hepatic homogenate. The histopathological analysis showed that the grade of liver injury was ameliorated with reduction of inflammatory cells and necrosis of liver cells in homoplantaginin treatment mice. These results suggest that homoplantaginin has a protective and therapeutic effect on hepatocyte injury, which might be associated with its antioxidant properties.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 06/2009; 47(7):1710-5. · 2.99 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Des-gamma-carboxy prothrombin (DCP) is an aberrant prothrombin produced by hepatocellular carcinoma (HCC) cells. Serum and tissue DCP expressions are thought to reflect the biological malignant potential of HCC. However, the role of DCP in the development of angiogenesis is not well understood. Herein, we report the effects of DCP on growth and migration of human vascular endothelial cells. DCP significantly stimulated the proliferation of HUVEC (ECV304) cells in a dose and time dependent manner, as measured by the MTT assay. A continuous rapid migration of ECV304 cells was observed in the presence of DCP measured by the scratch wound assay. The continuous rapid invasive activity, measured by transwell chamber assay also showed that DCP increased endothelial cells migration through the reconstituted extracellular matrix (Matrigel). Further, the tube formation of vascular endothelial cells on 3-D Matrigel showed an increased number of branch points of ECV304 cells induced by DCP in a dose dependent manner. The levels of vascular endothelial cell growth-related angiogenic factors and matrix metalloproteinase were also examined. DCP significantly stimulated the expression levels of epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and matrix metalloproteinase (MMP)-2 (latent and active). Together, these data suggest that DCP is a novel type of vascular endothelial growth factor that possesses potent mitogenic and migrative activities in angiogenesis of HCC.
    Clinical and Experimental Metastasis 04/2009; 26(5):469-77. · 3.46 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Microtubules are long-standing targets in cancer chemotherapy. Previously, we reported that marchantin C triggers apoptosis of human tumor cells. We show here that marchantin C induced cell cycle arrest at G(2)/M phase in A172 and HeLa cells. In addition, marchantin C decreased the quantity of microtubules in a time- and dose-dependent manner in these cells. Exposure of purified bovine brain tubulin to marchantin C inhibited polymerization of gross tubulin in vitro. Moreover, marchantin C potently suppressed the growth of human cervical carcinoma xenografts in nude mice. Marchantin C-treated xenografts showed decreased microtubules, Bcl-2 and increased cyclin B1, Bax, caspase-3, indicating that marchantin C possess the same ability to induce microtubules depolymerization and tumor cell apoptosis in tumor-bearing mice as in vitro. In conclusion, marchantin C is a novel microtubule inhibitor that induces mitotic arrest of tumor cells and suppresses tumor cell growth, exhibiting promising antitumor therapeutic potential.
    Cancer letters 04/2009; 276(2):160-70. · 5.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Des-gamma-carboxyl prothrombin (DCP) is a serum protein produced by hepatocellular carcinoma (HCC) cells. The aim of this study was to evaluate the angiogenic activity of DCP in HCC cells. The proliferation of HCC cells was measured by 3-[4, 5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay. The growth of HCC cells was also evaluated in vivo by using the xenografts in nude mice. The enzyme-linked immunosorbent assay (ELISA) was employed to measure the levels of angiogenic factors in supernatant of cell culture. The expression of angiogenic factors was examined by Western blot analysis and immunohistochemical staining. DCP displayed the stimulation of HCC cell growth in a dose (5-80 ng/ml) and time (24-96 h) dependent manner. The increase of cell growth was also observed in nude mice bearing well-established, palpable HepG2 and SMMC-7721 xenografts after 2 weeks administration of DCP. HCC cell growth was accompanied by the elevated levels of angiogenic factors. The levels of vascular endothelial growth factor (VEGF), transforming growth factor-alpha (TGF-alpha) and basic fibroblast growth factor (bFGF) in supernatant of SMMC-7721 cells were increased from 47, 126, and 60 pg/10(6) cells/24 h to 400, 208, and 298 pg/10(6) cells/24 h, respectively, after 72 h incubation with 80 ng/ml of DCP. The results of Western blot analysis and immunohistochemical staining of HCC xenografts also showed the significant increase of VEGF, TGF-alpha, and bFGF in HCC cells. These results provide the information that DCP is a type of growth factor in progression of HCC.
    Life Sciences 01/2009; 83(23-24):815-20. · 2.56 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Matrix metalloproteinase (MMP)-2 and MMP-9 have been associated with the ability of tumor cells to metastasize because of their capacity to degrade type IV collagen, the main component of basement membrane, and to their elevated expression in malignant tumors. (S)-methyl 6-(benzyloxycarbonylamino)-2-(2-((S)-2,6-dioxo-3-(3,4,5-trimethoxybenzamido) piperidin-1-yl) acetamido) hexanoate (CH1104I) is a galloyl cyclic-imide derivative designed to fit and extend into the S1' active pocket of MMP-2 and MMP-9. We aimed to evaluate the efficacy of CH1104I as a candidate compound for antiinvasion and antimetastasis of tumor cells. CH1104I significantly blocked gelatinase activity as evidenced by a decrease in the degradation of succinylated gelatin. Gelatin zymography analysis showed that the compound (7-210 micromol/l) inhibited the activity of MMP-2 and MMP-9 produced by human ovarian carcinoma SKOV3 cells. Inhibition of MMP-2 and MMP-9 expression was also observed using the assays of immunocytochemical staining and western blot analysis. The results showed that CH1104I suppressed the expression of zymogens and active MMP-2 and MMP-9. The effects of CH1104I on the invasion and migration of SKOV3 cells were then measured. Both the trans-well motility assay and wound scratch assay indicated that CH1104I was very effective for the antiinvasion and antimigration of SKOV3 cells. Furthermore, the Lewis lung carcinoma model was used to evaluate the efficacy of CH1104I in vivo. A significant inhibition of pulmonary metastasis of carcinoma cells was observed in CH1104I-administrated mice (25-100 mg/kg). These results suggest that CH1104I is a potential MMP-2 and MMP-9 inhibitor that may effectively suppress tumor invasion and metastasis.
    Anti-Cancer Drugs 12/2008; 19(10):957-65. · 2.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Des-gamma-carboxy prothrombin (DCP) is a serum protein produced by hepatocellular carcinoma (HCC) cells in the absence of vitamin K. Serum and tissue DCP expressions are thought to reflect the biological malignant potential of HCC. Hence, we aimed to examine the efficacy of vitamin K(2) on the production of DCP as well as tumor cell growth and invasion. Cell growth and viability were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. The in vivo efficacy of vitamin K(2) was examined in nude mice bearing HCC cells. A 24-well transwell chamber was used to evaluate the motility and invasive ability of HCC cells. Levels of DCP in supernatant of cultures and in serum of mice were measured using an electrochemiluminescence immunoassay method. Western blot and immunohistochemical analysis were employed to evaluate the expression of DCP in HCC. Vitamin K(2) (2-40 muM) significantly decreased the levels of DCP production in supernatant of PLC/PRF/5 and HepG2 cells and in serum of nude mice bearing HCC xenografts. The inhibition of DCP was also observed using the assays of Western blot analysis in HCC cultures and immunohistochemical analysis in HCC xenografts in mice. As a result of administration of vitamin K(2), the capacity of HCC growth was inhibited and the invasion and migration of tumor cells were decreased. Furthermore, the inhibitory effects of HCC growth were also observed in vivo and the sensitivity was well correlated with the decrease of DCP in the serum of mice. Vitamin K(2) might suppress the growth and invasion of HCC cells via decrease of DCP.
    Chemotherapy 11/2008; 55(1):28-35. · 2.07 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: QA1 and QA3 are the derivatives of substituted 1,3-dimethyl-1H-quinoxalin-2-ones that may selectively antagonize P-glycoprotein (P-gp) in multidrug resistance (MDR) cancer cells. Herein, we examined the reversal effect of two compounds on MDR in adriamycin (Adr)-induced resistant K562/A02 cells. MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide) assay showed that QA1 and QA3 weakly inhibited the growth of tumor cells. However, the compounds increased Adr-induced cytotoxicity toward K562/A02 cells. The IC(50) values of Adr toward K562/A02 were decreased in the presence of QA1 or QA3. The maximal reversal fold (RF) of QA1 and QA3 was reached 6.9 and 9.0, respectively. The action of QA1 and QA3 was also confirmed by the increase of intracellular Adr accumulation in K562/A02 cells. In mechanism study, the intracellular accumulation and efflux of Rh123 were measured using multilabel counter with excitation/emission wavelengths of 485/535nm. An increase of intracellular Rh123 and the decrease of efflux were observed in K562/A02 cells incubation with QA1 or QA3, indicating that the activity of P-gp was blocked. These results suggested that the derivatives of substituted 1,3-dimethyl-1H-quinoxalin-2-ones might reverse MDR in K562/A02 cells via inhibition activity of P-gp. QA1 and QA3 might be the candidate agents for reversing MDR of cancer.
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 09/2008; 63(3):202-8. · 2.24 Impact Factor

Publication Stats

159 Citations
62.19 Total Impact Points

Institutions

  • 2012
    • University of Jinan (Jinan, China)
      Chi-nan-shih, Shandong Sheng, China
  • 2009–2012
    • School of Pharmaceutical Sciences of Shandong
      Chi-nan-shih, Shandong Sheng, China
  • 2007–2011
    • Shandong University
      • • Department of Pharmacology
      • • School of Pharmaceutical Sciences
      Jinan, Shandong Sheng, China