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Article

Cell Culture Characterization of Prooxidative Chain-Transfer Agents as Novel Cytostatic Drugs

1
Evolutionary Biochemistry and Redox Medicine, Institute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg University, 55128 Mainz, Germany
2
Institute for Translational Medicine, MSH Medical School Hamburg, 20457 Hamburg, Germany
*
Author to whom correspondence should be addressed.
Academic Editors: Višnja Stepanić and Marta Kučerová-Chlupáčová
Molecules 2021, 26(21), 6743; https://doi.org/10.3390/molecules26216743
Received: 8 October 2021 / Revised: 1 November 2021 / Accepted: 4 November 2021 / Published: 8 November 2021
(This article belongs to the Special Issue Redox Active Molecules in Cancer Treatments)
Prooxidative therapy is a well-established concept in infectiology and parasitology, in which prooxidative drugs like artemisinin and metronidazole play a pivotal clinical role. Theoretical considerations and earlier studies have indicated that prooxidative therapy might also represent a promising strategy in oncology. Here, we have investigated a novel class of prooxidative drugs, namely chain-transfer agents, as cytostatic agents in a series of human tumor cell lines in vitro. We have found that different chain-transfer agents of the lipophilic thiol class (like dodecane-1-thiol) elicited half-maximal effective concentrations in the low micromolar range in SY5Y cells (human neuroblastoma), Hela cells (human cervical carcinoma), HEK293 cells (immortalized human kidney), MCF7 cells (human breast carcinoma), and C2C12 cells (mouse myoblast). In contrast, HepG2 cells (human hepatocellular carcinoma) were resistant to toxicity, presumably through their high detoxification capacity for thiol groups. Cytotoxicity was undiminished by hypoxic culture conditions, but substantially lowered after cellular differentiation. Compared to four disparate, clinically used reference compounds in vitro (doxorubicin, actinomycin D, 5-fluorouracil, and hydroxyurea), chain-transfer agents emerged as comparably potent on a molar basis and on a maximum-effect basis. Our results indicate that chain-transfer agents possess a promising baseline profile as cytostatic drugs and should be explored further for anti-tumor chemotherapy. View Full-Text
Keywords: chain-transfer agent; chemotherapy; free radical chain reaction; lipid peroxidation; lipophilic thiol; oxidative cell death; prooxidative drug; radical propagation; rate-limiting step chain-transfer agent; chemotherapy; free radical chain reaction; lipid peroxidation; lipophilic thiol; oxidative cell death; prooxidative drug; radical propagation; rate-limiting step
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MDPI and ACS Style

Heymans, V.; Kunath, S.; Hajieva, P.; Moosmann, B. Cell Culture Characterization of Prooxidative Chain-Transfer Agents as Novel Cytostatic Drugs. Molecules 2021, 26, 6743. https://doi.org/10.3390/molecules26216743

AMA Style

Heymans V, Kunath S, Hajieva P, Moosmann B. Cell Culture Characterization of Prooxidative Chain-Transfer Agents as Novel Cytostatic Drugs. Molecules. 2021; 26(21):6743. https://doi.org/10.3390/molecules26216743

Chicago/Turabian Style

Heymans, Victoria, Sascha Kunath, Parvana Hajieva, and Bernd Moosmann. 2021. "Cell Culture Characterization of Prooxidative Chain-Transfer Agents as Novel Cytostatic Drugs" Molecules 26, no. 21: 6743. https://doi.org/10.3390/molecules26216743

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