Doxorubicin (DOX) is a potent anticancer agent that binds both DNA and cardiolipin (CL). To investigate DOX binding to CL versus DNA

 

Abstract

Doxorubicin (DOX) is a potent anticancer agent that binds both DNA and cardiolipin (CL). To investigate DOX binding to CL versus DNA, aqueous soluble, CL-enriched nanoparticles, termed nanodisks (ND), were employed. Upon incubation with CL-ND, but not with phosphatidylcholine ND, DOX binding was detected. DOX binding to CL-ND was sensitive to buffer pH and ionic strength. To investigate if a DOX binding preference for DNA versus CL-ND exists, an agarose gel-based dye binding assay was developed. Under conditions wherein the commercial fluorescent dye, GelRed, detects a 636 bp DNA template following electrophoresis, DOX staining failed to visualize this DNA band. Incubation of the template DNA with DOX prior to electrophoresis resulted in a DOX concentration-dependent attenuation of GelRed staining intensity. When the template DNA was pre-incubated with equivalent amounts of free DOX or DOX-CL-ND, no differences in the extent of GelRed staining intensity attenuation were noted. When DOX was incubated with DNA alone, or a mixture of DNA and CL-ND, the extent of DOX-induced GelRed staining intensity attenuation was equivalent. Thus, DOX has a binding preference for DNA versus CL and, moreover, DOX-CL-ND offer a potential strategy to prevent DOX-induced cardiotoxicity while not affecting its affinity for DNA.

PMID: 32045568 [PubMed - as supplied by publisher]

12:13

Photo

Not included, change data exporting settings to download.

256×256, 6.0 KB

12:13

In reply to this message

pubmed: ctoall&ca or conall

Side-effects profile and outcomes of ponatinib in the treatment of chronic myeloid leukemia.

Related Articles

Side-effects profile and outcomes of ponatinib in the treatment of chronic myeloid leukemia.

Blood Adv. 2020 Feb 11;4(3):530-538

Authors: Chan O, Talati C, Isenalumhe L, Shams S, Nodzon L, Fradley M, Sweet K, Pinilla-Ibarz J