Regulatory Mechanism on Anti-Glycolytic and Anti-Metastatic Activities Induced by <i>Strobilanthes crispus</i> in Breast Cancer, In Vitro
An active fraction of <i>S. crispus</i>, 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 me...
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| Main Authors: | , , , |
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| Format: | Book |
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MDPI AG,
2023-01-01T00:00:00Z.
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| Summary: | An active fraction of <i>S. crispus</i>, 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<sub>50</sub> 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. |
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| Item Description: | 10.3390/ph16020153 1424-8247 |