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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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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Title: The Vascular Disrupting Agent Combretastatin A-4 Phosphate Causes Prolonged Elevation of Proteins Involved in Heme Flux and Function in Resistant Tumor Cells
Author(s):
Dey, Sanchareeka;
Kumari, Sharda;
Kalainayakan, Sarada Preeta;
Campbell, James,,III;
Ghosh, Poorva;
Zhou, Heling;
FitzGerald, Keely E.;
Li, Maoping;
Mason, Ralph P.;
Zhang, Li;
Liu, Li
Date Created: 2017-12-28
Item Type: article
Keywords: Show Keywords
Abstract: Vascular 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.
Publisher: Impact Journals LLC
ISSN: 1949-2553
Source: Oncotarget
Link to Related Resource: http://dx.doi.org/10.18632/oncotarget.23734
Persistent Link: http://hdl.handle.net/10735.1/6213
Bibliographic Citation: Dey, 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.23734
Terms of Use: CC BY 3.0 (Attribution)
©2017 The Authors
Sponsors: The 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).

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CC BY 3.0 (Attribution) Except where otherwise noted, this item's license is described as CC BY 3.0 (Attribution)