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Cytotoxic effects o...
Cytotoxic effects of intra and extracellular zinc chelation on human breast cancer cells
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- Hashemi, Mohammad (författare)
- Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
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- Ghavami, Saeid (författare)
- Department of Biochemistry and Medical Genetics, Manitoba Institute of Cell Biology, Cancer Care Manitoba, Winnipeg, Manitoba, Canada; Department of Clinical Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
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- Eshraghi, Mehdi (författare)
- Manitoba Institute of Cell Biology, and Department of Biochemistry and Medical Genetics, Univ. Manitoba, Winnipeg, Canada
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- Booy, Evan P. (författare)
- Manitoba Institute of Cell Biology, and Department of Biochemistry and Medical Genetics, Univ. Manitoba, Winnipeg, Canada
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- Los, Marek Jan (författare)
- Manitoba Institute of Cell Biology, Cancer Care Manitoba; Manitoba Institute of Child Health; Department of Biochemistry and Medical Genetics; Department of Human Anatomy and Cell Science, University Manitoba, Winnipeg, Canada,
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(creator_code:org_t)
- Elsevier BV, 2007
- 2007
- Engelska.
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Ingår i: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999 .- 1879-0712. ; 557:1, s. 9-19
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https://liu.diva-por... (primary) (Raw object)
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http://liu.diva-port...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Zinc is an essential trace element with cofactor functions in a large number of proteins of intermediary metabolism, hormone secretion pathways, immune defence mechanisms, and as a cofactor of transcription factors it is also involved in the control of gene expression. Our study demonstrates that the modulation of intra and extracellular zinc alone is sufficient to induce metabolic changes or even apoptosis in two model human breast cancer cell lines MCF-7 and MDA-MB468. Treatment of breast cancer cells with different concentrations of a cell membrane permeable zinc chelator, N,N,N'N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) and the membrane impermeable zinc chelator, diethylenctriaminepentacetic acid, (DTPA) resulted in a significant increase of cell death. Features of apoptosis, such as chromatin condensation and nuclear fragmentation accompanied the DTPA and TPEN-induced cell death. A significant increase in the activity of caspase-9 was observed in both cell lines; whereas, caspase-3 activity was only increased in MDA-MB468 cells since caspase-3 is not expressed in MCF-7 cells. Caspase-8 activation was negligible in both cell lines. Addition of Zn2+ or Cu2+ prevented DTPA and TPEN-induced cytotoxicity, indicating that both bivalent cations can be replaced functionally to a certain extent in our experimental system. Interestingly, addition of Ca2+, or Mg2+ had no effect. The antioxidant N-Acetyl-L-Cysteine inhibited the cytotoxic effect of DTPA and TPEN, indicating that oxidative stress is the likely mediator of Zn-deficiency-related cell death. (c) 2006 Elsevier B.V. All rights reserved.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Nyckelord
- airway epithelial-cells
- Apoptosis
- apoptotic protease
- Breast cancer
- caspase
- caspase activation
- Cu/Zn-dismutase
- cytochrome-c
- deficiency
- diethylenetriaminepentacetic acid
- dna-damage
- in-vitro
- intracellular zinc
- lipid-peroxidation
- metal-ions
- N '
- N
- ' N ' N '-tetrakis(2-pyridylmethyl)ethylenediamine
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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