The Vascular Disrupting Agent Combretastatin A-4 Phosphate Causes Prolonged Elevation of Proteins Involved in Heme Flux and Function in Resistant Tumor Cells

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dc.contributor.authorDey, Sanchareekaen_US
dc.contributor.authorKumari, Shardaen_US
dc.contributor.authorKalainayakan, Sarada Preetaen_US
dc.contributor.authorCampbell, James,,IIIen_US
dc.contributor.authorGhosh, Poorvaen_US
dc.contributor.authorZhou, Helingen_US
dc.contributor.authorFitzGerald, Keely E.en_US
dc.contributor.authorLi, Maopingen_US
dc.contributor.authorMason, Ralph P.en_US
dc.contributor.authorZhang, Lien_US
dc.contributor.authorLiu, Lien_US
dc.contributor.utdAuthorDey, Sanchareekaen_US
dc.contributor.utdAuthorKalainayakan, Sarada Preetaen_US
dc.contributor.utdAuthorGhosh, Poorvaen_US
dc.contributor.utdAuthorFitzGerald, Keely E.en_US
dc.contributor.utdAuthorZhang, Lien_US
dc.date.accessioned2018-10-22T19:31:27Z
dc.date.available2018-10-22T19:31:27Z
dc.date.created2017-12-28en_US
dc.date.issued2018-10-22
dc.description.abstractVascular disrupting agents (VDAs) represent a promising class of anti-cancer drugs for solid tumor treatment. Here, we aim to better understand the mechanisms underlying tumor reccurrence and treatment resistance following the administration of a VDA, combretastatin A-4 phosphate (CA4P). Firstly, we used photoacoustic tomography to noninvasively map the effect of CA4P on blood oxygen levels throughout subcutaneous non-small cell lung cancer (NSCLC) tumors in mice. We found that the oxygenation of peripheral tumor vessels was significantly decreased at 1 and 3 hours post-CA4P treatment. The oxygenation of the tumor core reduced significantly at 1 and 3 hours, and reached anoxia after 24 hours. Secondly, we examined the effect of CA4P on the levels of proteins involved in heme flux and function, which are elevated in lung tumors. Using immunohistochemistry, we found that CA4P substantially enhanced the levels of enzymes involved in heme biosynthesis, uptake, and degradation, as well as oxygen-utilizing hemoproteins. Furthermore, measurements of markers of mitochondrial function suggest that CA4P did not diminish mitochondrial function in resistant tumor cells. These results suggest that elevated levels of heme flux and function contribute to tumor regrowth and treatment resistance post-VDA administration.en_US
dc.description.departmentSchool of Natural Sciences and Mathematicsen_US
dc.description.sponsorshipThe Cancer Prevention and Research Institute of Texas (RP 160617, RP 140399, RP 120670-P3); National Institute of Health Shared Instrumentation grants (1S10RR024757 and S10 OD018094).en_US
dc.identifier.bibliographicCitationDey, Sanchareeka, Sharda Kumari, Sarada Preeta Kalainayakan, James,,III Campbell, et al. 2018. "The vascular disrupting agent combretastatin A-4 phosphate causes prolonged elevation of proteins involved in heme flux and function in resistant tumor cells." Oncotarget 9(3), doi:10.18632/oncotarget.23734en_US
dc.identifier.issn1949-2553en_US
dc.identifier.issue3en_US
dc.identifier.urihttp://hdl.handle.net/10735.1/6213
dc.identifier.volume9en_US
dc.language.isoenen_US
dc.publisherImpact Journals LLCen_US
dc.relation.urihttp://dx.doi.org/10.18632/oncotarget.23734
dc.rightsCC BY 3.0 (Attribution)en_US
dc.rights©2017 The Authorsen_US
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/en_US
dc.sourceOncotarget
dc.subjectCombretastatin A4 Phosphateen_US
dc.subjectBioluminescenceen_US
dc.subjectCancer--Statisticsen_US
dc.subjectXenograftsen_US
dc.subjectOncologyen_US
dc.subjectLungs--Tumorsen_US
dc.subjectHemeen_US
dc.subjectLung Neoplasmsen_US
dc.subjectHeterograftsen_US
dc.titleThe Vascular Disrupting Agent Combretastatin A-4 Phosphate Causes Prolonged Elevation of Proteins Involved in Heme Flux and Function in Resistant Tumor Cellsen_US
dc.type.genrearticleen_US

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