ReferenceID 2607
Phorbol 12-Myristate 13-Acetate Induced Toxicity Study and the Role of Tangeretin in Abrogating HIF-1α-NF-κB Crosstalk In Vitro and In Vivo
Int J Mol Sci
Phorbol 12-myristate 13-acetate (PMA) is a potent tumor promoter and highly inflammatory in nature. Here, we investigated the toxic effects of PMA on different model system. PMA (10 mug) caused chromosomal aberrations on
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Record Fields
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- Reference Id
- 2607
- Evidence Id
- 19197
- Core Evidence Id
- 19197
- Source Reference Id
- 5216
- Herb2 Reference Id
- HBREF006013
- Subject Paper Key
- HBIN039602_33291656
- Pubmed Id
- 33291656
- Doi
- 10.3390/ijms21239261
- Paper Title
- Phorbol 12-Myristate 13-Acetate Induced Toxicity Study and the Role of Tangeretin in Abrogating HIF-1α-NF-κB Crosstalk In Vitro and In Vivo
- Paper Abstract
- Phorbol 12-myristate 13-acetate (PMA) is a potent tumor promoter and highly inflammatory in nature. Here, we investigated the toxic effects of PMA on different model system. PMA (10 mug) caused chromosomal aberrations on the Allium cepa root tip and induced mitotic dysfunction. Similarly, PMA caused embryonic and larval deformities and a plummeted survivability rate on zebrafish embryo in a dose-dependent manner. Persistently, PMA treatment on immortalized human keratinocyte human keratinocyte (HaCaT) cells caused massive inflammatory rush at 4 h and a drop in cell survivability at 24 h. Concomitantly, we replicated a cutaneous inflammation similar to human psoriasis induced by PMA. Herein, we used tangeretin (TAN), as an antagonist to counteract the inflammatory response. Results from an in vivo experiment indicated that TAN (10 and 30 mg/kg) significantly inhibited PMA stimulated epidermal hyperplasia and intra-epidermal neutrophilic abscesses. In addition, its treatment effectively neutralized PMA induced elevated reactive oxygen species (ROS) generation on in vitro and in vivo systems, promoting antioxidant response. The association of hypoxia-inducible factor 1-alpha (HIF-1alpha)-nuclear factor kappa-light-chain-enhancer of activated b cells (NF-kappaB) crosstalk triggered by PMA enhanced PKCalpha-ERK1/2-NF-kappaB pathway; its activation was also significantly counteracted after TAN treatment. Conclusively, we demonstrated TAN inhibited the nuclear translocation of HIF-1alpha and NF-kappaB p65. Collectively, TAN treatment ameliorated PMA incited malignant inflammatory response by remodeling the cutaneous microenvironment.
- Journal
- Int J Mol Sci
- Publish Year
- 2020
- Experiment Subject
- human; immortalized human keratinocyte human keratinocyte (hacat) cells
- Experiment Type
- Clinical & Cell Experiment
- Phenotype Related
- Intra-epidermal Neutrophilic Abscesses; Psoriasis; Tumor; Epidermal Hyperplasia; Mitotic Dysfunction; Embryonic And Larval Deformities; Cutaneous Inflammation
- Paper Title Cn
- Paper Title En
- Phorbol 12-Myristate 13-Acetate Induced Toxicity Study and the Role of Tangeretin in Abrogating HIF-1α-NF-κB Crosstalk In Vitro and In Vivo
- Bilingual Status
- semi_complete