ReferenceID 3585
Hispidulin Enhances TRAIL-Mediated Apoptosis via CaMKK/AMPK/USP51 Axis-Mediated Bim Stabilization
Cancers (Basel)
Hispidulin, a natural compound present in herbs, has anti-cancer effects. Here, we investigated whether hispidulin sensitizes human carcinoma cells to apoptosis induced by TRAIL. Sub-lethal dosages of TRAIL alone and hi
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Record Fields
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- Reference Id
- 3585
- Evidence Id
- 20175
- Core Evidence Id
- 20175
- Source Reference Id
- 937
- Herb2 Reference Id
- HBREF001638
- Subject Paper Key
- HBIN024094_31817696
- Pubmed Id
- 31817696
- Doi
- 10.3390/cancers11121960
- Paper Title
- Hispidulin Enhances TRAIL-Mediated Apoptosis via CaMKK/AMPK/USP51 Axis-Mediated Bim Stabilization
- Paper Abstract
- Hispidulin, a natural compound present in herbs, has anti-cancer effects. Here, we investigated whether hispidulin sensitizes human carcinoma cells to apoptosis induced by TRAIL. Sub-lethal dosages of TRAIL alone and hispidulin alone does not increase apoptosis, but hispidulin increases sensitivity to TRAIL, resulting in induction of apoptosis in hispidulin plus TRAIL-treated cancer cells. In addition, combined treatment with hispidulin and TRAIL also reduced tumor growth and increased apoptosis in xenograft models. However, hispidulin did not alter cell viability in human renal normal mesangial cells and human skin fibroblast. Hispidulin markedly increased the BH3-only proteins Bim at the post-translational levels. Depletion of Bim with siRNA significantly blocked hispidulin plus TRAIL-induced apoptosis. Furthermore, we found that activation of AMPK by hispidulin has a crucial role in Bim proteins stability through up-regulation of USP51 expression. Our findings suggest that USP51-dependent stabilization of Bim by AMPK activation plays a critical role in hispidulin-mediated sensitization of cancer cells to apoptosis induced by TRAIL.
- Journal
- Cancers (Basel)
- Publish Year
- 2019
- Experiment Subject
- xenograft models
- Experiment Type
- Animal Experiment
- Phenotype Related
- Cancer
- Paper Title Cn
- Paper Title En
- Hispidulin Enhances TRAIL-Mediated Apoptosis via CaMKK/AMPK/USP51 Axis-Mediated Bim Stabilization
- Bilingual Status
- semi_complete