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HDL‐Associated Proteins and LDL Differentially Modulate Chronic Myelogenous Leukemia Cell Viability
Author(s) -
Andersen Catherine J.,
Murray Kristina,
Ragonesi Nicholas,
Doerr Adam,
CintronRivera Layra,
Dupree Lydia
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.653.11
Subject(s) - abca1 , viability assay , abcg1 , efflux , scavenger receptor , cholesterol , chemistry , cd36 , pharmacology , chronic myelogenous leukemia , k562 cells , biology , cell , biochemistry , leukemia , receptor , transporter , immunology , lipoprotein , gene
HDL has been shown to exert anti‐cancer effects. One of the mechanisms by which HDL impairs cancer cell growth is through mediation of cellular cholesterol and phospholipid efflux, thereby limiting the availability of essential lipids for rapidly proliferating cells. Cholesterol efflux is facilitated through interactions between cellular ATP‐binding cassette transporter A1 (ABCA1) and apolipopotein A1 (apoA1), in addition to efflux via ABCG1, scavenger receptor class B type 1 (SR‐BI), and passive diffusion to lipidated HDL. Efflux can further be regulated serum amyloid A (SAA), a pro‐inflammatory acute phase protein shown to be elevated in cancer, infection, and obesity. Despite the ability of SAA to displace apoA1 on HDL, studies have reported SAA to both increase and decrease cholesterol efflux. In this study, we investigated the effects of lipoproteins (HDL and LDL) and HDL‐associated proteins (apoA1 and SAA) on chronic myelogenous leukemia cell viability. K562 cells were cultured in the presence of human HDL or LDL (10, 25, or 50 ug/mL) for 24 hours, then assessed for viability. While no changes in K562 cell viability were observed with HDL treatment, LDL dose‐dependently increased cell viability. We further examined the effects of lipoproteins on K562 viability in the presence of the liver X receptor (LXR) agonist TO901317 (5 uM), which is known to induce expression of HDL‐related transporters. Accordingly, we observed significantly increased expression of ABCA1 at 24hr and 72hr following TO901317 treatment. Interestingly, the addition of HDL to TO901317‐treated cells did not affect K562 cell viability, whereas LDL dose‐dependently increased viability. Conversely, treatment of cells with human‐derived apoA1 or HDL + apoA1 drastically reduced K562 cell viability after 48hr and 72hr. K562 cell viability was modestly decreased by SAA treatment, with greater decreases observed in cells treated with SAA + HDL. These findings suggest that HDL‐associated proteins and LDL differentially regulate chronic myelogenous leukemia cell viability Support or Funding Information The Science Institute of the College of Arts and Sciences and Faculty Research Committee, Fairfield University