ReferenceID 3111
Usnic acid induces apoptosis in human gastric cancer cells through ROS generation and DNA damage and causes up-regulation of DNA-PKcs and γ-H2A.X phosphorylation
Chem Biol Interact
Usnic acid, a dibenzofuran derivative found in many lichen species, is reported to have anticancer activity against human gastric cancer. We investigated the molecular alterations associated with anticancer effects of us
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Record Fields
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- Reference Id
- 3111
- Evidence Id
- 19701
- Core Evidence Id
- 19701
- Source Reference Id
- 6214
- Herb2 Reference Id
- HBREF007011
- Subject Paper Key
- HBIN047633_31715134
- Pubmed Id
- 31715134
- Doi
- 10.1016/j.cbi.2019.108898
- Paper Title
- Usnic acid induces apoptosis in human gastric cancer cells through ROS generation and DNA damage and causes up-regulation of DNA-PKcs and γ-H2A.X phosphorylation
- Paper Abstract
- Usnic acid, a dibenzofuran derivative found in many lichen species, is reported to have anticancer activity against human gastric cancer. We investigated the molecular alterations associated with anticancer effects of usnic acid against human gastric adenocarcinoma AGS and gastric carcinoma SNU-1 cells. Usnic acid (10-25 muM) treatment to these cells caused a significant increase in mitochondrial membrane depolarization and apoptotic cells. Apoptosis induction was accompanied by an increase in the ratio of Bax:Bcl-2 expression and cleaved-PARP. Usnic acid increased the comet tail length and tail DNA in alkaline comet assay indicating DNA double-strand breaks which was also evidenced by an increase in gammaH2A.X (Ser139) phosphorylation. The expression of DNA damage response proteins including DNA-PKcs, pATM (Ser1981), Chk-2 and p53 were increased. Further, N-acetyl cysteine, a known reactive oxygen species (ROS) scavenger, reversed the effects of usnic acid on expression of DNA damage response proteins and gammaH2A.X (Ser139) phosphorylation. This reversal was also observed in comet assay in a time and dose-dependent manner suggesting that usnic acid-induced DNA damage was caused by ROS. In addition, the non-toxic concentrations (1-10 muM) of usnic acid inhibited colony forming potential of AGS cells indicating its anti-proliferation activity. More importantly, the concentration of usnic acid that caused significant death in gastric cancer cells, did not show any considerable toxicity to normal human embryonic kidney HEK293 cells, human keratinocyte HaCaT cells and mouse primary gastric cells. Collectively, these results for the first time demonstrated the selective apoptotic effect of usnic acid (10-25 muM) through ROS generation and DNA damage on human gastric cancer cells accompanied with upregulation of gammaH2A.X (Ser139) phosphorylation, DNA-PKcs and p53.
- Journal
- Chem Biol Interact
- Publish Year
- 2020
- Experiment Subject
- mouse; human; ags cells; human gastric adenocarcinoma ags and gastric carcinoma snu-1 cells; human keratinocyte hacat cells; normal human embryonic kidney hek293 cells
- Experiment Type
- Cell Experiment
- Phenotype Related
- Gastric Carcinoma; Gastric Cancer; Gastric Adenocarcinoma
- Paper Title Cn
- Paper Title En
- Usnic acid induces apoptosis in human gastric cancer cells through ROS generation and DNA damage and causes up-regulation of DNA-PKcs and γ-H2A.X phosphorylation
- Bilingual Status
- semi_complete