ReferenceID 4477

Amentoflavone inhibits tumor necrosis factor-α-induced migration and invasion through AKT/mTOR/S6k1/hedgehog signaling in human breast cancer

Food Funct

Inflammatory cytokine tumor necrosis factor-alpha (TNFalpha) has been demonstrated to accelerate the progression and metastasis of various carcinomas. In this study, we investigated the effect of amentoflavone on inhibit

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Reference Id
4477
Evidence Id
21067
Core Evidence Id
21067
Source Reference Id
2236
Herb2 Reference Id
HBREF003033
Subject Paper Key
HBIN015834_34542136
Pubmed Id
34542136
Doi
10.1039/d1fo01085a
Paper Title
Amentoflavone inhibits tumor necrosis factor-α-induced migration and invasion through AKT/mTOR/S6k1/hedgehog signaling in human breast cancer
Paper Abstract
Inflammatory cytokine tumor necrosis factor-alpha (TNFalpha) has been demonstrated to accelerate the progression and metastasis of various carcinomas. In this study, we investigated the effect of amentoflavone on inhibiting the migration and invasion of TNFalpha-induced breast cancer cells. Results showed that amentoflavone significantly blocked the cellular migration and invasion of MCF10DCIS.com and MDA-MB-231 cells at a concentration of 10 muM but did not affect the cell viability. The mRNA and protein levels of matrix metalloproteinase (MMP)-9, significantly activated by TNFalpha, were reversed by amentoflavone treatment in a dose-dependent manner in MCF10DCIS.com cells. Congruent with the protein level, the activity of MMP-9 was significantly suppressed by amentoflavone treatment. Additionally, we found that amentoflavone dampened Gli1-dependent noncanonical hedgehog signaling, which is a key factor in the regulation of migration and invasion in TNFalpha-induced human breast cancer cells. Further study elucidated that TNFalpha enhanced Gli1 through the activation of the AKT/mTOR/S6K1 cascade, whereas it receded after amentoflavone treatment in human breast cancer cells. In summary, amentoflavone abrogated Gli1 activation in TNFalpha-induced mammary tumor cells, resulting in a decrease of invasiveness in human breast cancer cells via mediating AKT/mTOR/S6K1 signaling. Amentoflavone should be considered as a potent food ingredient for the retardation of mammary tumorigenesis.
Journal
Food Funct
Publish Year
2021
Experiment Subject
human; mcf10dcis.com; mcf10dcis.com cells; mda-mb-231 cells; tnfalpha-induced breast cancer cells; tnfalpha-induced mammary tumor cells
Experiment Type
Cell Experiment
Phenotype Related
Carcinomas; Inflammatory Cytokine Tumor; Breast Cancer; Tnfalpha-induced Mammary Tumor
Paper Title Cn
Paper Title En
Amentoflavone inhibits tumor necrosis factor-α-induced migration and invasion through AKT/mTOR/S6k1/hedgehog signaling in human breast cancer
Bilingual Status
semi_complete