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Keywords = carba-dimer

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17 pages, 3606 KiB  
Article
Hydrogen Peroxide Mediates Artemisinin-Derived C-16 Carba-Dimer-Induced Toxicity of Human Cancer Cells
by 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 2020, 9(2), 108; https://doi.org/10.3390/antiox9020108 - 26 Jan 2020
Cited by 5 | Viewed by 4055
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 [...] Read more.
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 (IC50) 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 G1-phase, suggesting a G1 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 H2DCF-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. Full article
(This article belongs to the Section Natural and Synthetic Antioxidants)
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