Relationship between copper, zinc and metallothionein in hepatocellular carcinoma and its surrounding liver parenchyma

Ebara, Masaaki; Fukuda, Hiroyuki; Hatano, Ryouji; Saisho, Hiromitsu; Nagato, Yoshinobu; Suzuki, Keiji; Nakajima, Katsuyuki; Yukawa, Masae; Kondo, Fukuo; Nakayama, Akihiro; Sakurai, Hiromu

doi:10.1016/s0168-8278(00)80277-9

Cited by 97 publications

(71 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Under these conditions, zinc plasma concentrations are normally reduced and copper levels are elevated (6). Similar observations have been reported in the liver tissue of patients with hepatocellular carcinoma (7).…”

Section: Introductionsupporting

confidence: 76%

Plasma concentrations of zinc, copper, interleukin-6 and interferon-γ, and plasma dipeptidyl peptidase IV activity in chronic hepatitis C

Grüngreiff¹

2008

Mol Med Rep

View full text Add to dashboard Cite

Section: Introductionsupporting

confidence: 76%

Plasma concentrations of zinc, copper, interleukin-6 and interferon-γ, and plasma dipeptidyl peptidase IV activity in chronic hepatitis C

Grüngreiff¹

2008

Mol Med Rep

View full text Add to dashboard Cite

“…It was found that in the presence of Cu (II) the calf thymus DNA was remarkably damaged by resveratrol and its analogues, and induced cytotoxicity in human leukemia HL-60 and Jurkat cell lines. These data were supported by Ebara et al (2000) which found that hepatocellular carcinoma have an accumulation of copper than that in the surrounding liver parenchyma. The accumulation of Cu and the present of metallothionein may be related to the carcinogenesis of HCC.…”

Section: Resultsmentioning

confidence: 57%

Anti-proliferative effect of pterostilbene on rat hepatoma cells in culture

2014

View full text Add to dashboard Cite

Pterostilbene, a methoxylated analogue of resveratrol, is a natural compound primarily found in blueberries and several types of grapes. However, little is known about the effect of pterostilbene on the proliferation of hepatoma cells and its modes of actions. This study was undertaken to characterize its ability to suppress the proliferation of hepatoma AH109A cells and the possible mechanism(s) involved. Pterostilbene showed a significant and dose-dependent effect on the anti-proliferative activity against AH109A cells. Pterostilbene exerted little or no effect on the proliferation of rat L6 myoblasts and rat skin fibroblasts. Pterostilbeneloaded rat sera could significantly inhibit the proliferation of AH109A cells, which suggests that pterostilbene could be absorbed through gastrointestinal tract and retain its anti-proliferative activity. Pterostilbene arrested the cell cycle of AH109A cells at G0/ G1 phase and reduced the protein expression of cyclindependent kinase 4 and cyclin-dependent kinase 6 dose-dependently. We also found that pterostilbene could significantly increase the intracellular peroxide level of AH109A cells, which may be involved in its anti-proliferative activity.

show abstract

“…Significantly downregulated genes were identified only at the higher copper concentrations (400 and 600 M) except for Negative regulation of apoptosis (10) IGF binding (3) Protein kinase inhibitor activity (5) LDL receptor activity (2) Regulation of erythrocyte differentiation (2) Muscle cell differentiation (3) Regulation of transcription (70) Oxygen and ROS metabolism (4) Ribosome assembly (3) Regulation of nitric oxide biosynthesis (2) Transcription corepressor activity (9) Ubiquitin-protein ligase activity (9) Response to stress (19) Calcium-dependent protein binding (3) Hemopoiesis (7) Cell cycle arrest (8) Peptidoglycan metabolism (3) Cell growth (14) Ribosome assembly (2) Endosome organization and biogenesis (2) GTPase activity (13) Kinase inhibitor activity (4) LDL receptor activity (3) Protein dimerization activity (24) Small GTPase-mediated signal transduction (21) Transcription corepressor activity (9) Transcription factor activity (68) Continued alanine hydroxylase (PAH) (organic acid metabolism); fibrinogen ␣-chain (FGA), fibrinogen ␤-chain (FGB), fibrinogen ␥-chain (FGG), erythropoietin (EPO), and angiopoietin-like 1 (AN-GPTL1) (circulation, coagulation, and wound healing); haptoglobin (HP) and haptoglobin-related protein (HPR) (hemoglobin binding); ankyrin repeat domain 15 (ANKRD15), BRCA1-associated RING 1 (BARD1), and centromere protein F (CENPF) (regulation of the cell cycle); and serpin peptidase inhibitor A4 (SERPINA4), serpin peptidase inhibitor I1 (SERPINI1), and reversion-inducing cysteine-rich protein with kazal motifs (RECK) (serine -type endopeptidase inhibitor activity) (Supplemental Material, Additional Data File 2).…”

Section: Gene Expression Profilementioning

confidence: 99%

“…Patients with these diseases present hepatic copper levels at milligram/gram concentrations (61). In addition to genetic disorders of copper metabolism, other pathological conditions, including hepatic necrosis, cholestatic cirrhosis, bile duct proliferation, hepatitis, and hepatocellular carcinoma, are associated with elevated copper levels (19,20,25). Environmental exposures to elevated copper levels have been reported to be as high as 160 M in drinking water and up to 90 mM in rivers (1).…”

mentioning

confidence: 99%

Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper

Song

Freedman

2009

Physiological Genomics

View full text Add to dashboard Cite

Copper is an essential trace element; however, at supraphysiological levels, it can be extremely toxic. Microarray data from HepG2 cells exposed to 100, 200, 400, and 600 μM copper for 4, 8, 12 and 24 h were generated and analyzed. Principal components, K-means, and hierarchical clustering, interactome, and pathway mapping analyses indicated that these exposure conditions induce physiological and toxicological changes in the HepG2 transcriptome. As a general trend, when the level of toxicity increases, the number and diversity of affected genes, Gene Ontology categories, regulatory pathways, and complexity of interactomes increase. Physiological responses to copper include transition metal ion binding and responses to stress/stimulus, whereas toxicological responses include apoptosis, morphogenesis, and negative regulation of biomolecule metabolism. The global gene expression profile was overlaid onto biomolecular interaction networks and signal transduction cascades using pathway mapping and interactome identification. This analysis indicated that copper modulates signal transduction pathways associated with MAPK, NF-κB, death receptor, IGF-I, hypoxia, IL-10, IL-2, IL-6, EGF, Toll-like receptor, protein ubiquitination, xenobiotic metabolism, leukocyte extravasation, complement and coagulation, and sonic hedgehog signaling. These results provide insights into the global and molecular mechanisms regulating the physiological and toxicological responses to metal exposure.

show abstract

Relationship between copper, zinc and metallothionein in hepatocellular carcinoma and its surrounding liver parenchyma

Cited by 97 publications

References 20 publications

Plasma concentrations of zinc, copper, interleukin-6 and interferon-γ, and plasma dipeptidyl peptidase IV activity in chronic hepatitis C

Plasma concentrations of zinc, copper, interleukin-6 and interferon-γ, and plasma dipeptidyl peptidase IV activity in chronic hepatitis C

Anti-proliferative effect of pterostilbene on rat hepatoma cells in culture

Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper

Contact Info

Product

Resources

About