Scavenger receptor class BI (SR-BI) mediates uptake of CPX-351 into K562 leukemia cells.

Abstract

PURPOSE:

CPX-351 is a liposomal formulation of cytarabine and daunorubicin encapsulated at a 5:1 molar ratio, for the treatment of acute myeloid leukemia. The Scavenger Receptor class B type I (SR-BI) plays an important role in mediating the uptake of high-density lipoproteins. The purpose of this study is to assess the role of the cell surface lipoprotein receptor SR-BI in the uptake of CPX-351 liposomes (Jazz Pharmaceuticals) into K562 leukemia cells.

METHODS:

K562 cells were pre-treated with 10 nM siRNA for 48 h and then treated with varying amount of CPX-351 for 24, 48 and 72 h. Cells were then collected and analyzed at 480/590 nm on a CytoFLEX Multicolour flow instrument to determine cellular uptake of daunorubicin. Experimental data were analyzed using two-way ANOVA with Bonferroni multiple comparisons. Significance was set at p < .05.

RESULTS:

K562 cells pre-treated with SR-BI siRNA for 48 h had a reduced SRB1 cell surface concentration (74-85%). Addition of CPX-351 at 10-50 nM followed by measurement of cellular daunorubicin at 48, 48 or 72 h showed a significantly lower percentage of daunorubicin positive population compared with control K562 cells (p < .05). There was significantly less daunorubicin taken up in the SR-BI knock-down cells across all drug concentrations and at all three time points, although there were no concentration-related trends.

CONCLUSIONS:

These preliminary studies suggest that SR-BI may be one potential mechanism by which CPX-351 is taken up into K562 cells.

• Authors: Yunyun Di, Ellen K Wasan, Jacqueline Cawthray, Kishor M Wasan
• Journal: Drug development and industrial pharmacy (Drug Dev Ind Pharm) Vol. 45 Issue 1 Pg. 21-26 (Jan 2019) ISSN: 1520-5762 [Electronic] England
• PMID: 30113235 (Publication Type: Journal Article)

Chemical References

• CPX-351
• RNA, Small Interfering
• Receptors, Scavenger
• SCARB1 protein, human
• Scavenger Receptors, Class B
• Cytarabine
• Daunorubicin

Topics

• Cell Membrane (drug effects, metabolism)
• Cytarabine (metabolism, pharmacology)
• Daunorubicin (metabolism, pharmacology)
• Humans
• K562 Cells
• RNA, Small Interfering (pharmacology)
• Receptors, Scavenger (metabolism)
• Scavenger Receptors, Class B (metabolism)