Приказ основних података о документу

dc.creatorWallace, David
dc.creatorSpandidos, Demetrios A.
dc.creatorTsatsakis, Aristidis
dc.creatorSchweitzer, Amie
dc.creatorĐorđević, Vladimir
dc.creatorBuha-Đorđević, Aleksandra
dc.date.accessioned2019-09-02T12:09:03Z
dc.date.available2019-09-02T12:09:03Z
dc.date.issued2019
dc.identifier.issn1107-3756
dc.identifier.urihttps://farfar.pharmacy.bg.ac.rs/handle/123456789/3265
dc.description.abstractPancreatic 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 M) 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 M was used. Non-linear analysis of the response curves revealed lethal concentration 50% (LC50) values for CdCl2 in the HPNE cells of 77 M compared to 42 M in the AsPC-1 cells (P lt 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.en
dc.publisherSpandidos Publ Ltd, Athens
dc.relationOSU - 154333-7
dc.rightsopenAccess
dc.sourceInternational Journal of Molecular Medicine
dc.subjectWarburg effecten
dc.subjectoxidative stressen
dc.subjectcadmiumen
dc.subjectglycolysisen
dc.subjectoxidative phosphorylationen
dc.subjectcytotoxicityen
dc.titlePotential interaction of cadmium chloride with pancreatic mitochondria: Implications for pancreatic canceren
dc.typearticle
dc.rights.licenseARR
dcterms.abstractWаллаце, Давид; Сцхwеитзер, Aмие; Спандидос, Деметриос A.; Ђорђевић, Владимир; Тсатсакис, Aристидис; Буха-Ђорђевић, Aлександра;
dc.citation.volume44
dc.citation.issue1
dc.citation.spage145
dc.citation.epage156
dc.citation.other44(1): 145-156
dc.citation.rankM22
dc.identifier.wos000472804600014
dc.identifier.doi10.3892/ijmm.2019.4204
dc.identifier.pmid31115542
dc.identifier.scopus2-s2.0-85067371135
dc.identifier.fulltexthttps://farfar.pharmacy.bg.ac.rs//bitstream/id/1840/3263.pdf
dc.type.versionpublishedVersion


Документи

Thumbnail

Овај документ се појављује у следећим колекцијама

Приказ основних података о документу