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Potential interaction of cadmium chloride with pancreatic mitochondria: Implications for pancreatic cancer

  • Authors:
    • David R. Wallace
    • Demetrios A. Spandidos
    • Aristidis Tsatsakis
    • Amie Schweitzer
    • Vladimir Djordjevic
    • Aleksandra Buha Djordjevic
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacology, School of Biomedical Science, Oklahoma State University Center for Health Sciences, Tulsa, OK 74107-1898, USA, Laboratory of Clinical Virology, School of Medicine, University of Crete, 71003 Heraklion, Greece, Department of Toxicology and Forensics, School of Medicine, University of Crete, 71003 Heraklion, Greece, First Surgical Clinic, Clinical Center of Serbia, 11000 Belgrade, Serbia, Department of Toxicology ‘Akademik Danilo Soldatović’, Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia
    Copyright: © Wallace et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 145-156
    |
    Published online on: May 21, 2019
       https://doi.org/10.3892/ijmm.2019.4204
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Abstract

Pancreatic cancer (PC) is insidious with a high mortality rate due to the lack of symptomology prior to diagnosis. Mitochondrial involvement in PC development is becoming accepted, and exposure to cadmium (Cd) is suspected of being a risk factor for the development of PC; however, the mechanisms involved remain unclear. In this study, we examined the role of Cd as a mitochondrial toxicant and whether alterations in mitochondrial function may be an underlying cause for the development of PC. In this study, cadmium chloride (CdCl2)‑mediated toxicity in hTERT‑HPNE and AsPC‑1 pancreatic cell lines was determined by MTT assay. We also investigated the release of LDH and the generation of free radicals. Mitochondrial toxicity assays were performed in media containing glucose (25 mM) or galactose (10 mM) and following exposure to CdCl2 (0‑100 µM) followed by MTT assay. For the confirmation of mitochondrial toxicity, we measured the release of ATP following exposure to CdCl2. Initial experiments confirmed that exposure to CdCl2 did not reduce the viability of either cell line until a concentration of >10 µM was used. Non‑linear analysis of the response curves revealed lethal concentration 50% (LC50) values for CdCl2 in the HPNE cells of 77 µM compared to 42 µM in the AsPC‑1 cells (P<0.01). The CdCl2‑mediated mitochondrial toxic effects were greater in the HPNE cells, suggesting a heightened sensitivity to the effects of CdCl2, not due to elevated oxidative stress. Increased mitochondrial toxic sensitivity was indicated by a 73.4% reduction in IC50 values in the HPNE cells cultured in galactose compared to culture in glucose media, whereas the AsPC‑1 cells exhibited a 58.8% reduction in IC50 values. In addition, the higher concentration of CdCl2 elicited a significant cell‑dependent effect on ATP release in both cell lines, suggestive of CdCl2 being a mitochondrial toxicant. Cell survival was unaffected following exposure to low concentrations of CdCl2; however, exposure did alter mitochondrial function (control cells > tumor cells). Therefore, the findings of this study indicate that the mitochondria may be a site of action for cadmium in promoting tumor development.
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Copy and paste a formatted citation
Spandidos Publications style
Wallace DR, Spandidos DA, Tsatsakis A, Schweitzer A, Djordjevic V and Djordjevic AB: Potential interaction of cadmium chloride with pancreatic mitochondria: Implications for pancreatic cancer. Int J Mol Med 44: 145-156, 2019.
APA
Wallace, D.R., Spandidos, D.A., Tsatsakis, A., Schweitzer, A., Djordjevic, V., & Djordjevic, A.B. (2019). Potential interaction of cadmium chloride with pancreatic mitochondria: Implications for pancreatic cancer. International Journal of Molecular Medicine, 44, 145-156. https://doi.org/10.3892/ijmm.2019.4204
MLA
Wallace, D. R., Spandidos, D. A., Tsatsakis, A., Schweitzer, A., Djordjevic, V., Djordjevic, A. B."Potential interaction of cadmium chloride with pancreatic mitochondria: Implications for pancreatic cancer". International Journal of Molecular Medicine 44.1 (2019): 145-156.
Chicago
Wallace, D. R., Spandidos, D. A., Tsatsakis, A., Schweitzer, A., Djordjevic, V., Djordjevic, A. B."Potential interaction of cadmium chloride with pancreatic mitochondria: Implications for pancreatic cancer". International Journal of Molecular Medicine 44, no. 1 (2019): 145-156. https://doi.org/10.3892/ijmm.2019.4204
Copy and paste a formatted citation
x
Spandidos Publications style
Wallace DR, Spandidos DA, Tsatsakis A, Schweitzer A, Djordjevic V and Djordjevic AB: Potential interaction of cadmium chloride with pancreatic mitochondria: Implications for pancreatic cancer. Int J Mol Med 44: 145-156, 2019.
APA
Wallace, D.R., Spandidos, D.A., Tsatsakis, A., Schweitzer, A., Djordjevic, V., & Djordjevic, A.B. (2019). Potential interaction of cadmium chloride with pancreatic mitochondria: Implications for pancreatic cancer. International Journal of Molecular Medicine, 44, 145-156. https://doi.org/10.3892/ijmm.2019.4204
MLA
Wallace, D. R., Spandidos, D. A., Tsatsakis, A., Schweitzer, A., Djordjevic, V., Djordjevic, A. B."Potential interaction of cadmium chloride with pancreatic mitochondria: Implications for pancreatic cancer". International Journal of Molecular Medicine 44.1 (2019): 145-156.
Chicago
Wallace, D. R., Spandidos, D. A., Tsatsakis, A., Schweitzer, A., Djordjevic, V., Djordjevic, A. B."Potential interaction of cadmium chloride with pancreatic mitochondria: Implications for pancreatic cancer". International Journal of Molecular Medicine 44, no. 1 (2019): 145-156. https://doi.org/10.3892/ijmm.2019.4204
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