Preclinical Evaluation of 4-Methylthiobutyl Isothiocyanate on Liver Cancer and Cancer Stem Cells with Different p53 Status

Lamy, Evelyn; Hertrampf, Anke; Herz, Corinna; Schüler, Julia; Erlacher, Miriam; Bertele, Daniela; Bakare, Adekunle A.; Wagner, Meike; Weiland, Timo; Lauer, Ulrich M.; Drognitz, Oliver; Huber, Roman; Rohn, Sascha; Giesemann, Torsten; Mersch-Sundermann, Volker

doi:10.1371/journal.pone.0070846

Cited by 19 publications

(20 citation statements)

References 49 publications

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“…It has to be taken into account that concentrations inducing cell toxicity were still very high. In a previous study, the IC 50 of 4-MTB-ITC was determined using the neutral red retention assay with 23.18 μM in HepG2 cells18. This ITC, again, is a 1000-fold more potent in inducing cell death as compared to the cytotoxicity observed with the nitrile 4-MTB-CN in the present study.…”

Section: Discussionsupporting

confidence: 58%

“…1) against human liver cancer (HepG2) cells was studied. Keeping the toxicity of the related ITC in mind1718, first investigations of the cytotoxicity of nitriles were carried out using concentrations ranging from 0.1 to 100 μM. However, these concentrations did not impact cell viability (data not shown).…”

Section: Resultsmentioning

confidence: 99%

“…Murine hepatocytes were obtained from 8–16 week-old, male C57BL6 mice (Charles River Laboratory, Sulzfeld, Germany) as described elsewhere18. The institutional and national guidelines for the care and use of animals were followed, and all experimental procedures were approved by the institutional Animal Care and Use Committee at the University of Freiburg according to § 8.I of the Animal Welfare Act.…”

Section: Methodsmentioning

confidence: 99%

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Cytotoxic and genotoxic potential of food-borne nitriles in a liver in vitro model

Kupke¹,

Herz

Hanschen

et al. 2016

Sci Rep

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Isothiocyanates are the most intensively studied breakdown products of glucosinolates from Brassica plants and well recognized for their pleiotropic effects against cancer but also for their genotoxic potential. However, knowledge about the bioactivity of glucosinolate-borne nitriles in foods is very poor. As determined by GC-MS, broccoli glucosinolates mainly degrade to nitriles as breakdown products. The cytotoxicity of nitriles in human HepG2 cells and primary murine hepatocytes was marginal as compared to isothiocyanates. Toxicity of nitriles was not enhanced in CYP2E1-overexpressing HepG2 cells. In contrast, the genotoxic potential of nitriles was found to be comparable to isothiocyanates. DNA damage was persistent over a certain time period and CYP2E1-overexpression further increased the genotoxic potential of the nitriles. Based on actual in vitro data, no indications are given that food-borne nitriles could be relevant for cancer prevention, but could pose a certain genotoxic risk under conditions relevant for food consumption.

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Section: Discussionsupporting

confidence: 58%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Cytotoxic and genotoxic potential of food-borne nitriles in a liver in vitro model

Kupke¹,

Herz

Hanschen

et al. 2016

Sci Rep

Self Cite

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“…Thus, HepG2 cells may be sensitive to the structurally similar sulforaphene and sulforaphane. Previous studies focused on the potential of several other isothiocyanates, such as sulforaphane, benzyl isothiocyanate, phenylethyl isothiocyanate, and erucin, to inhibit proliferation and induce apoptosis in liver cancer cells [ 24 , 31 , 33 ]. Furthermore, in Sangthong’s study [ 30 ], a comparative cytotoxic analysis of the crude extract of Raphanus sativus and pure sulforaphene on liver cancer cells was performed, but their effect on apoptosis was not evaluated.…”

Section: Discussionmentioning

confidence: 99%

Induction of Apoptosis and Cytotoxicity by Isothiocyanate Sulforaphene in Human Hepatocarcinoma HepG2 Cells

et al. 2018

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Glucoraphenin, a glucosinolate present in large quantities in radish is hydrolysed by myrosinase to form the isothiocyanate sulforaphene, which is believed to be responsible for its chemopreventive activity; however, the underlying mechanisms of action have not been investigated, particularly in human cell lines. The aim of the study is to assess the cytotoxicity of sulforaphene in HepG2 cells and evaluate its potential to enhance apoptosis. The cytotoxicity of sulforaphene in HepG2 cells was carried out ensuing an initial screening with two other cell lines, MFC-7 and HT-29, where sulforaphene displayed highest toxicity in HepG2 cells following incubation at 24, 48 and 72 h. In contrast, the intact glucosinolate showed no cytotoxicity. Morphological studies indicated that sulforaphene stimulated apoptosis as exemplified by cell shrinkage, blebbing, chromatin condensation, and nuclear fragmentation. The Annexin V assay revealed significant increases in apoptosis and the same treatment increased the activity of caspases -3/7 and -9, whereas a decline in caspase-8 was observed. Impairment of cell proliferation was indicated by cell cycle arrest at the Sub G0/G1 phase as compared to the other phases. It may be concluded that sulforaphene, but not its parent glucosinolate, glucoraphenin, causes cytotoxicity and stimulates apoptosis in HepG2 cells.

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“…ITCs) are responsible for carcinogenic inhibition observed after exposure (13). Additionally ITCs have been demonstrated to retard or prevent the growth of tumour cells in vitro and in vivo (14). There are various ITCs, some of which include allyl-ITC (AITC), found in cabbage, benzyl-ITC (BITC) and phenylhexyl-ITC (PHITC) found in watercress, and sulforphane in broccoli and cauliflower (4).…”

mentioning

confidence: 99%

Natural and Synthetic Isothiocyanates Possess Anticancer Potential Against Liver and Prostate Cancer In Vitro

et al. 2019

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Background/Aim: Isothiocyanates (ITCs) are phytochemicals with potential cancer-preventative properties derived from the breakdown of glucosinolates that exist in cruciferous vegetables. Studies, to date, have demonstrated that various ITCs possess the ability to act as anticancer agents in different cancer types. This study investigated the anticancer properties of dietary ITCs (allyl-ITC, benzyl-ITC, phenylethyl-ITC) and synthetic (phenylbutyl-ITC and phenylhexyl-ITC) on liver and prostate carcinoma cells in vitro. Materials and Methods: The effects of ITCs on cellular viability, migration, invasion, clonogenicity, apoptosis induction and reactive oxygen species generation were assessed in HepG2, DU145 and 22Rv1 cells. Results: All ITCs reduced metabolic activity in each cell line with the most significant being phenylethyl-ITC. Both dietary and synthetic ITCs suppressed the migratory and invasive potential of all cell lines, inhibited colony-forming capability and induced apoptosis. Phenylethyl-ITC exposure resulted in the significant generation of reactive oxygen species. Conclusion: These data highlight the potential advantages of utilizing ITCs to delay the carcinogenic process and the potential for dietary and synthetic ITCs to act as anticancer agents.

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Preclinical Evaluation of 4-Methylthiobutyl Isothiocyanate on Liver Cancer and Cancer Stem Cells with Different p53 Status

Cited by 19 publications

References 49 publications

Cytotoxic and genotoxic potential of food-borne nitriles in a liver in vitro model

Cytotoxic and genotoxic potential of food-borne nitriles in a liver in vitro model

Induction of Apoptosis and Cytotoxicity by Isothiocyanate Sulforaphene in Human Hepatocarcinoma HepG2 Cells

Natural and Synthetic Isothiocyanates Possess Anticancer Potential Against Liver and Prostate Cancer In Vitro

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