| Autor: |
Muhammad SNH; Department of Chemical Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia., Safuwan NAM; Department of Chemical Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia., Yaacob NS; Department of Chemical Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia., Fauzi AN; Department of Chemical Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, Malaysia. |
| Jazyk: |
angličtina |
| Zdroj: |
Pharmaceuticals (Basel, Switzerland) [Pharmaceuticals (Basel)] 2023 Jan 20; Vol. 16 (2). Date of Electronic Publication: 2023 Jan 20. |
| DOI: |
10.3390/ph16020153 |
| Abstrakt: |
An active fraction of S. crispus , F3, and its bioactive compounds (lutein, β-sitosterol, and stigmasterol) were reported to have anti-glycolytic activities in MDA-MB-231 cells. Since glycolysis can also regulate metastatic activities in cancer cells, this study investigated the mechanism underlying the anti-glycolytic and anti-metastatic activities induced by F3 and its bioactive compounds on MDA-MB-231 cells. The cells were treated with IC 50 concentrations of F3, lutein, β-sitosterol, and stigmasterol. GLUT1 protein expression and localization were then observed using a fluorescence microscope. We found that F3, lutein, and β-sitosterol inhibit localization of GLUT1 to the cell membrane, which causes the decrease in glucose uptake. This is supported by a reduction in PKC activity, measured using a spectrophotometer, and increased TXNIP protein expression detected by Western blotting. Both TXNIP and PKC are involved in GLUT1 activation and localization. The expression of signaling proteins involved in the PI3K/AKT pathway was also measured using a flow cytometer. Results show that F3, lutein, β-sitosterol, and stigmasterol reduced the expression of AKT, pAKT, mTOR, and HIF1α in MDA-MB-231 cells. Transwell migration assay was used to measure migration of the MDA-MB-231 cells. A reduction in fibronectin protein expression was observed by fluorescence microscopy, after treatments with F3 and its bioactive compounds, leading to a reduction in the MDA-MB-231 cells' migratory abilities. As a conclusion, F3 acts as a metabolic inhibitor by inhibiting metabolic rewiring in the promotion of cancer metastasis, potentially due to the presence of its bioactive compounds. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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