ReferenceID 2490
Topoisomerase poisoning by the flavonoid nevadensin triggers DNA damage and apoptosis in human colon carcinoma HT29 cells
Arch Toxicol
Nevadensin, an abundant polyphenol of basil, is reported to reduce alkenylbenzene DNA adduct formation. Furthermore, it has a wide spectrum of further pharmacological properties. The presented study focuses the impact of
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- Reference Id
- 2490
- Evidence Id
- 19080
- Core Evidence Id
- 19080
- Source Reference Id
- 4985
- Herb2 Reference Id
- HBREF005782
- Subject Paper Key
- HBIN036835_34635930
- Pubmed Id
- 34635930
- Doi
- 10.1007/s00204-021-03162-5
- Paper Title
- Topoisomerase poisoning by the flavonoid nevadensin triggers DNA damage and apoptosis in human colon carcinoma HT29 cells
- Paper Abstract
- Nevadensin, an abundant polyphenol of basil, is reported to reduce alkenylbenzene DNA adduct formation. Furthermore, it has a wide spectrum of further pharmacological properties. The presented study focuses the impact of nevadensin on topoisomerases (TOPO) in vitro. Considering the DNA-intercalating properties of flavonoids, first, minor groove binding properties (IC50 = 31.63 microM), as well as DNA intercalation (IC50 = 296.91 microM) of nevadensin, was found. To determine potential in vitro effects on TOPO I and TOPO IIalpha, the relaxation and decatenation assay was performed in a concentration range of 1-500 microM nevadensin. A partial inhibition was detected for TOPO I at concentrations >= 100 microM, whereas TOPO IIalpha activity is only inhibited at concentrations >= 250 microM. To clarify the mode of action, the isolating in vivo complex of enzyme assay was carried out using human colon carcinoma HT29 cells. After 1 h of incubation, the amount of TOPO I linked to DNA was significantly increased by nevadensin (500 microM), why nevadensin was characterized as TOPO I poison. However, no effects on TOPO IIalpha were detected in the cellular test system. As a subsequent cellular response to TOPO I poisoning, a highly significant increase of DNA damage after 2 h and a decrease of cell viability after 48 h at the same concentration range were found. Furthermore, after 24 h of incubation a G2/M arrest was observed at concentrations >= 100 microM by flow cytometry. The analysis of cell death revealed that nevadensin induces the intrinsic apoptotic pathway via activation of caspase-9 and caspase-3. The results suggest that cell cycle disruption and apoptotic events play key roles in the cellular response to TOPO I poisoning caused by nevadensin in HT29 cells.
- Journal
- Arch Toxicol
- Publish Year
- 2021
- Experiment Subject
- human; ht29 cells; human colon carcinoma ht29 cells
- Experiment Type
- Cell Experiment
- Phenotype Related
- Colon Carcinoma
- Paper Title Cn
- Paper Title En
- Topoisomerase poisoning by the flavonoid nevadensin triggers DNA damage and apoptosis in human colon carcinoma HT29 cells
- Bilingual Status
- semi_complete