Hydrogen Peroxide Mediates Artemisinin-Derived C-16 Carba-Dimer-Induced Toxicity of Human Cancer Cells

Amanda L. Kalen; Brett A. Wagner; Ehab H. Sarsour; Maneesh G. Kumar; Jessica L. Reedy; Garry R. Buettner; Nabin C. Barua; Prabhat C. Goswami

doi:10.3390/antiox9020108

Back

Hydrogen Peroxide Mediates Artemisinin-Derived C-16 Carba-Dimer-Induced Toxicity of Human Cancer Cells

Journal article

Open access

Peer reviewed

Hydrogen Peroxide Mediates Artemisinin-Derived C-16 Carba-Dimer-Induced Toxicity of Human Cancer Cells

Amanda L. Kalen, Brett A. Wagner, Ehab H. Sarsour, Maneesh G. Kumar, Jessica L. Reedy, Garry R. Buettner, Nabin C. Barua and Prabhat C. Goswami

Antioxidants, Vol.9(2), p.108

01/26/2020

DOI: 10.3390/antiox9020108

PMCID: PMC7070254

PMID: 31991904

Files and links (1)

url

https://doi.org/10.3390/antiox9020108View

Published (Version of record) Open Access

Abstract

This study used a nitroaliphatic chemistry approach to synthesize a novel artemisinin-derived carba-dimer (AG-1) and determined its anti-proliferative effects in human normal and cancer cells. AG-1 treatments selectively inhibit proliferation of cancer cells compared to normal human fibroblasts. Compared to artemisinin, AG-1 is more toxic to human breast, prostate, head–neck, pancreas and skin cancer cells; 50% inhibition (IC 50 ) 123 µM in AG-1 vs. 290 µM in artemisinin-treated breast cancer cells. AG-1 treatment decreased (~5 folds) cyclin D1 protein expression that correlated with an increase in the percentage of cells in the G 1 -phase, suggesting a G 1 delay. AG-1-induced toxicity was independent of the DNA damage at 72 h post-treatment, as measured by micronuclei frequency and γH2AX protein levels. Results from electron paramagnetic resonance spectroscopy showed Fe-catalyzed formation of AG-1 carbon-centered radicals in a cell-free system. Flow cytometry analysis of H 2 DCF-DA oxidation showed a significant increase in the steady-state levels of reactive oxygen species (ROS) in AG-1-treated cells. Pre-treatment with N -acetyl- l -cysteine and antioxidant enzymes (superoxide dismutase and catalase) significantly suppressed AG-1-induced toxicity, suggesting that superoxide and hydrogen peroxide contribute to AG-1-induced toxicity in human cancer cells. AG-1 represents a novel class of anti-cancer drug that is more potent than its parent compound, artemisinin.

aliphatic nitro chemistry

artemisinin

carba-dimer

cyclin D1

oxidative stress

Details

Title: Subtitle: Hydrogen Peroxide Mediates Artemisinin-Derived C-16 Carba-Dimer-Induced Toxicity of Human Cancer Cells
Creators: Amanda L. Kalen - University of Iowa
Brett A. Wagner - University of Iowa
Ehab H. Sarsour - Kansas City University
Maneesh G. Kumar - University of Iowa
Jessica L. Reedy - Radiation Oncology Branch, Center for Cancer Research, National Cancer Institutes of Health, Bethesda, MD 20892, USA.
Garry R. Buettner - University of Iowa
Nabin C. Barua - North East Institute of Science and Technology
Prabhat C. Goswami - University of Iowa
Resource Type: Journal article
Publication Details: Antioxidants, Vol.9(2), p.108
DOI: 10.3390/antiox9020108
PMID: 31991904
PMCID: PMC7070254
NLM abbreviation: Antioxidants (Basel)
ISSN: 2076-3921
eISSN: 2076-3921
Publisher: MDPI
Grant note: DOI: 10.13039/100000009, name: National Institutes of Health, award: P30 CA086862
Language: English
Date published: 01/26/2020
Academic Unit: Radiation Oncology
Record Identifier: 9984313072102771

Metrics

43 Record Views

5 Times Cited - Web of Science

See more details