Distribution of trace metal concentrations in paired cancerous and non-cancerous human stomach tissues

Yaman, Mehmet; Kaya, Gökçe; Yekeler, Hayrettin

doi:10.3748/wjg.v13.i4.612

Cited by 91 publications

(55 citation statements)

References 28 publications

(43 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Any shift toward non-favorable concentrations will disrupt the metal homeostasis, causing severe damage at the cellular level. 2 In comparison to normal tissues, many types of tumors have elevated levels of copper and zinc, both of which are known to contribute to the process of carcinogenesis. 3 Such tumors include breast, cervical, ovarian, lung, prostate, stomach and leukemias.…”

Section: Introductionmentioning

confidence: 99%

Chk1 and DNA-PK mediate TPEN-induced DNA damage in a ROS dependent manner in human colon cancer cells

Rahal

Fatfat

Hankache

et al. 2016

Cancer Biology & Therapy

View full text Add to dashboard Cite

Recently, we showed that the metal chelator TPEN targets colon cancer cells through redox cycling of copper. Here, we studied the DNA damage potential of TPEN and deciphered the role of Chk1, ATM and DNA-PK in TPEN-induced toxicity in 3 human colon cancer cell lines, HCT116, SW480 and HT29. We also investigated the role of reactive oxygen species (ROS) in TPEN-induced DNA damage. TPEN reduced cell viability in a dose-and time-dependent manner. Cytotoxicity was associated with significant DNA damage and higher expression of g-H2AX protein and activation of ATM/ATR signaling pathway. Cell death by TPEN was dependent on ROS generation as evidenced by the reversal of cell viability, and DNA damage and the abrogation of g-H2AX levels in the presence of antioxidants. Treatment with antioxidants, however, failed to reverse cytotoxicity at high TPEN concentrations (10mM). TPEN-induced cell death was also dependent on the redox cycling of copper since the copper chelator neocuproine inhibited DNA damage and reduced pChk1, g-H2AX, and ATM protein expression. Cell death by low TPEN concentrations, involved ATM/ATR signaling in all 3 cell lines, since pre-incubation with specific inhibitors of ATM and DNA-PK led to the recovery of cells from TPEN-induced DNA damage. In addition, siRNA silencing of Chk1, DNA-PK and ATM abrogated the expression of g-H2AX and reversed cell death, suggesting that Chk1 and DNA-PK mediate TPEN-induced cytotoxicity in colon cancer cells. This study shows for the first time the involvement of Chk1, DNA-PK and ATM in TPEN-induced DNA damage and confirms our previous findings that ROS generation and the redox cycling of copper in response to TPEN are the main mechanisms by which this compound induces cell death in human colon cancer cells. Inhibition of ATM or DNA-PK did not reverse cytotoxicity at high TPEN concentrations that cause excessive levels of ROS and irreversible cellular damage.Abbreviations: ROS, reactive oxygen species; XIAP, X-linked inhibitor of apoptosis; DNA-PK, DNA-dependent protein kinase; ATM, ataxia telangiectasia mutated; ATR, serine/threonine protein kinase ataxia telangiectasia; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; DCFH, 2 0 ,7 0 -Dichlorofluorescin diacetate; NAC, N-acetyL-cysteine; CAT, catalase; DSB, double strand break; SSB, single strand break; Neo, neocuproine; PI, propidium iodide; DDR, DNA damage response

show abstract

Section: Introductionmentioning

confidence: 99%

Chk1 and DNA-PK mediate TPEN-induced DNA damage in a ROS dependent manner in human colon cancer cells

Rahal

Fatfat

Hankache

et al. 2016

Cancer Biology & Therapy

View full text Add to dashboard Cite

show abstract

“…CuSO 4 . The BM has been systematically applied onto apricot trees since the end of the 20 th century.…”

Section: +mentioning

confidence: 99%

“…The coppers and complexes found in some foods cannot be dissolved by stomach acids or cannot be completely absorbed into the bloodstream from the small intestine [2,[4][5].…”

Section: Introductionmentioning

confidence: 99%

“…Data collected by speciation provides significant information about how elements are metabolized as well as their toxicity and bioavailability. Thereby, total element content must be evaluated by considering not only determination of element activity, but also its chemical and physical form, concentration and oxidation steps [1][2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Fractionation and Speciation of Cu in Different Processing Apricots

Erdoğan¹,

Erdemoğlu²,

Güçer³

2017

J Nutr Food Sci

View full text Add to dashboard Cite

An analytical procedure was proposed to study the operational fraction of Cu in ripe-fresh, sun-dried and sulphited-dried apricots harvested from either treated Bordeaux mixture or unexposed trees. Based on the methods that consists pressurized liquid extraction procedure and solid phase extraction to separate diverse Cu fractions on different sorbents such as Dowex 50Wx8-40 and Amberlite XAD-7, and then flame atomic absorption spectrometry (FAAS) and ion selective electrode were used for off-line determination of Cu concentrations in the effluents obtained.Total copper concentrations in different processing the apricot samples exposed to Bordeaux mixture were 4.58, 4.48 and 4.25 µg/g in ripe fresh, sun-dried, sulphuring-sun drying, respectively. However, Cu concentrations in the organic apricot samples were determined 2.92; 2.97 and 2.25 µg/g. While circa 40-59% of total copper are extractable with water solvent including about 67-68% cationic copper, 25-33% organically bound copper and 26-44% labile in Kabaaşı apricot samples. Besides, while about 27-48% of total copper are extractable with methanol: water solvents containing about 40-23% cationic copper, 60-78% organically bound copper and 56-71% of copper was absorbed in the stomach.It was applied to analytical procedures for Cu speciation in the apricot samples were verified and validated.

show abstract

“…Another metal, Cd, has been reported to inhibit thyroid function and induce thyroid dysfunction (Buha et al 2013;Gupta et al 1997;Gupta and Kar 1999). Furthermore, there is literature data supporting the hypothesis that the direct influence of toxic heavy metals, for example manganese (Mn), copper (Cu), and Zn, on thyrocytes plays a role in thyroid cancer etiology (Yaman et al 2007). …”

Section: Introductionmentioning

confidence: 99%

T-screen and yeast assay for the detection of the thyroid-disrupting activities of cadmium, mercury, and zinc

Liu

Ren

et al. 2016

Environ Sci Pollut Res

View full text Add to dashboard Cite

In the present study, a two-hybrid yeast bioassay and a T-screen were used to screen for the thyroid receptor (TR)-disrupting activity of select metallic compounds (CdCl 2 , ZnCl 2 , HgCl 2 , CuSO 4 , MnSO 4 , and MgSO 4 ). The results reveal that none of the tested metallic compounds showed TRagonistic activity, whereas ZnCl 2 , HgCl 2 , and CdCl 2 demonstrated TR antagonism. For the yeast assay, the dose-response relationship of these metallic compounds was established, and the concentrations producing 20 % of the maximum effect of ZnCl 2 , HgCl 2 , and CdCl 2 were 9.1 × 10 −5 , 3.2 × 10 −6 , and 1.2 × 10 −6 mol/L, respectively. The T-screen also supported the finding that ZnCl 2 , HgCl 2 , and CdCl 2 decreased the cell proliferation at concentrations ranging from 10 −6 to 10 −4 mol/ L. Furthermore, the thyroid-disrupting activity of metallic compounds in environmental water samples collected from the Guanting Reservoir, Beijing, China was evaluated. Solid-phase extraction was used to separate the organic extracts, and a modified two-hybrid yeast bioassay revealed that the metallic compounds in the water samples could affect thyroid hormone-induced signaling by decreasing the binding of the thyroid hormone. The addition of ethylenediaminetetraacetic acid (30 mg/L) could eliminate the effects. Thus, the cause(s) of the thyroid toxicity in the water samples appeared to be partly related to the metallic compounds.

show abstract

Distribution of trace metal concentrations in paired cancerous and non-cancerous human stomach tissues

Abstract: In contrast to the literature data for Cu and Fe, the concentrations of copper, iron and nickel in cancerous tissue samples are higher than those in the non-cancerous samples. Furthermore, the Ca levels are lower in cancerous tissue samples than in non-cancerous tissue samples.

Cited by 91 publications

References 28 publications

Chk1 and DNA-PK mediate TPEN-induced DNA damage in a ROS dependent manner in human colon cancer cells

Chk1 and DNA-PK mediate TPEN-induced DNA damage in a ROS dependent manner in human colon cancer cells

Fractionation and Speciation of Cu in Different Processing Apricots

T-screen and yeast assay for the detection of the thyroid-disrupting activities of cadmium, mercury, and zinc

Contact Info

Product

Resources

About