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

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 s...

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Autores principales:	Victoria Heymans, Sascha Kunath, Parvana Hajieva, Bernd Moosmann
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	chain-transfer agent chemotherapy free radical chain reaction lipid peroxidation lipophilic thiol oxidative cell death Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/074c42c1873c4593b5b28f5f4fea2c84
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spelling	oai:doaj.org-article:074c42c1873c4593b5b28f5f4fea2c842021-11-11T18:40:47ZCell Culture Characterization of Prooxidative Chain-Transfer Agents as Novel Cytostatic Drugs10.3390/molecules262167431420-3049https://doaj.org/article/074c42c1873c4593b5b28f5f4fea2c842021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6743https://doaj.org/toc/1420-3049Prooxidative 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.Victoria HeymansSascha KunathParvana HajievaBernd MoosmannMDPI AGarticlechain-transfer agentchemotherapyfree radical chain reactionlipid peroxidationlipophilic thioloxidative cell deathOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6743, p 6743 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	chain-transfer agent chemotherapy free radical chain reaction lipid peroxidation lipophilic thiol oxidative cell death Organic chemistry QD241-441
spellingShingle	chain-transfer agent chemotherapy free radical chain reaction lipid peroxidation lipophilic thiol oxidative cell death Organic chemistry QD241-441 Victoria Heymans Sascha Kunath Parvana Hajieva Bernd Moosmann Cell Culture Characterization of Prooxidative Chain-Transfer Agents as Novel Cytostatic Drugs
description	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.
format	article
author	Victoria Heymans Sascha Kunath Parvana Hajieva Bernd Moosmann
author_facet	Victoria Heymans Sascha Kunath Parvana Hajieva Bernd Moosmann
author_sort	Victoria Heymans
title	Cell Culture Characterization of Prooxidative Chain-Transfer Agents as Novel Cytostatic Drugs
title_short	Cell Culture Characterization of Prooxidative Chain-Transfer Agents as Novel Cytostatic Drugs
title_full	Cell Culture Characterization of Prooxidative Chain-Transfer Agents as Novel Cytostatic Drugs
title_fullStr	Cell Culture Characterization of Prooxidative Chain-Transfer Agents as Novel Cytostatic Drugs
title_full_unstemmed	Cell Culture Characterization of Prooxidative Chain-Transfer Agents as Novel Cytostatic Drugs
title_sort	cell culture characterization of prooxidative chain-transfer agents as novel cytostatic drugs
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/074c42c1873c4593b5b28f5f4fea2c84
work_keys_str_mv	AT victoriaheymans cellculturecharacterizationofprooxidativechaintransferagentsasnovelcytostaticdrugs AT saschakunath cellculturecharacterizationofprooxidativechaintransferagentsasnovelcytostaticdrugs AT parvanahajieva cellculturecharacterizationofprooxidativechaintransferagentsasnovelcytostaticdrugs AT berndmoosmann cellculturecharacterizationofprooxidativechaintransferagentsasnovelcytostaticdrugs
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Cell Culture Characterization of Prooxidative Chain-Transfer Agents as Novel Cytostatic Drugs

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