Artesunate acts through cytochrome c to inhibit growth of pediatric AML cells

Kristen S Hill; Erin E Schuler; Sally R Ellingson; Jill M Kolesar

doi:10.1038/s41598-023-49928-y

Back

Artesunate acts through cytochrome c to inhibit growth of pediatric AML cells

Journal article

Open access

Peer reviewed

Artesunate acts through cytochrome c to inhibit growth of pediatric AML cells

Kristen S Hill, Erin E Schuler, Sally R Ellingson and Jill M Kolesar

Scientific reports, Vol.13(1), 22383

12/16/2023

DOI: 10.1038/s41598-023-49928-y

PMCID: PMC10725448

PMID: 38104159

Files and links (1)

url

https://doi.org/10.1038/s41598-023-49928-yView

Published (Version of record) Open Access

Abstract

Artesunate is a derivative of artemisinin, an active compound isolated from Artemisia annua which has been used in Traditional Chinese Medicine and to treat malaria worldwide. Artemisinin derivatives have exhibited anti-cancer activity against both solid tumors and leukemia. The direct target(s) of artesunate are controversial; although, heme-bound proteins in the mitochondria have been implicated. We utilized computational modeling to calculate the predicted binding score of artesunate with heme-bound mitochondrial proteins and identified cytochrome c as potential artesunate target. UV-visible spectroscopy showed changes in the absorbance spectrum, and thus protein structure, when cytochrome c was incubated with artesunate. Artesunate induces apoptosis, disrupts mitochondrial membrane potential, and is antagonized by methazolamide in pediatric AML cells indicating a probable mechanism of action involving cytochrome c. We utilized a multi-disciplinary approach to show that artesunate can interact with and is dependent on cytochrome c release to induce cell death in pediatric AML cell lines.

Antimalarials - pharmacology

Antimalarials - therapeutic use

Artemisinins - pharmacology

Artesunate - pharmacology

Child

Cytochromes c

Heme

Humans

Leukemia, Myeloid, Acute - drug therapy

Details

Title: Subtitle: Artesunate acts through cytochrome c to inhibit growth of pediatric AML cells
Creators: Kristen S Hill - Markey Cancer Center
Erin E Schuler - University of Kentucky
Sally R Ellingson - Markey Cancer Center
Jill M Kolesar - University of Kentucky
Resource Type: Journal article
Publication Details: Scientific reports, Vol.13(1), 22383
DOI: 10.1038/s41598-023-49928-y
PMID: 38104159
PMCID: PMC10725448
ISSN: 2045-2322
eISSN: 2045-2322
Grant note: P30CA177558 / NIH HHS P30 CA177558 / NCI NIH HHS
Language: English
Date published: 12/16/2023
Academic Unit: Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics
Record Identifier: 9984696554902771

Metrics

12 Record Views

3 Times Cited - Web of Science

See more details