In a glial-cell comparison, 50 μM fenofibrate for 72 h produced greater cell death in glioblastoma models than in normal human astrocytes. Normal astrocytes nevertheless showed cell death and acute respiration inhibition, so these experiments demonstrate relative susceptibility rather than complete tumor specificity. [2]
PPARα reporter activation depends on FABP context
Cell-based study · COS-7 cells transfected with human PPARα, PPRE3-TK-LUC and β-galactosidase, with empty vector, FABP1 or FABP2 [1]
Fenofibrate increased reporter activity in PPARα-expressing cells. FABP2 enhanced this response; FABP1 did not significantly enhance it. The separate fenofibric-acid comparator showed a different FABP dependence. Ligands had no effect without PPARα.
Literature-Reported Treatment Conditions
- Treatment concentration
- 50 μM fenofibrate; separate comparator: 50 μM fenofibric acid
- Exposure duration
- 24 h treatment, starting 24 h after transfection
- Method
- Luciferase activity normalized using β-galactosidase; compared with vehicle and no-FABP/empty-vector controls
- Vehicle
- 0.1% v/v DMSO
- Co-treatment
- No drug combination; FABP1 or FABP2 co-expression was an experimental factor.
Methods and source locations
Compound reported in the paper: Fenofibrate; Compound label in the paper: Fenofibrate
Evidence applies to the paper’s tested fenofibrate material and models; no equivalence to a particular Adooq lot is established.
Figure 5B–C,E and caption; Results: ligand-dependent PPARα transcription; Experimental Procedures: PPARα luciferase reporter assay and Materials
PPARα reporter activity following fenofibrate: Values described in Results; Figure 5 shows mean ± S.E. from four independent experiments; *p < 0.05 versus PPARα alone. No exact error values inferred from bars. — Figure 5B–C,E and caption; Results: ligand-dependent PPARα transcription; Experimental Procedures: PPARα luciferase reporter assay and Materials
Separate fenofibric-acid reporter comparator: Distinct acid comparator at 50 μM for 24 h in the same reporter design; not a fenofibrate potency value. — Figure 5B–C,E and caption; Results: ligand-dependent PPARα transcription; Experimental Procedures: PPARα luciferase reporter assay and Materials
Acute respiration inhibition persists after PPARα perturbation
Cell-based study · LN-229 human glioblastoma cells with PPARα-targeting or scrambled siRNA, or GW6471 pretreatment [2]
Acute fenofibrate addition reduced oxygen consumption despite PPARα knockdown or antagonist pretreatment. These controls support a PPARα-independent component of the acute mitochondrial response, without establishing that every later fenofibrate effect is receptor-independent.
Literature-Reported Treatment Conditions
- Treatment concentration
- 50 μM fenofibrate; pretreatment: 100 nM PPARα-targeting siRNA or scrambled siRNA, or 1 μM GW6471
- Exposure duration
- 48 h pretreatment followed by acute fenofibrate injection and real-time flux monitoring
- Method
- Extracellular flux OCR/ECAR assay; PPARα mRNA knockdown checked by qPCR
- Vehicle
- DMSO; matching DMSO and scrambled-siRNA controls
- Co-treatment
- Fenofibrate tested after PPARα knockdown or GW6471 pretreatment; antagonist-alone controls included.
Methods and source locations
Compound reported in the paper: Fenofibrate; Compound label in the paper: FF
Evidence applies to the paper’s tested fenofibrate material and models; no equivalence to a particular Adooq lot is established.
Figure 7A–B and caption; Results paragraph beginning “To verify further”; Materials and methods: Cell culture and Evaluation of metabolic parameters
Acute oxygen consumption after fenofibrate: Figure 7A–B: mean ± SD from two separate experiments in triplicate (n=6); caption marks DMSO-versus-FF differences, P ≤ 0.05 explicitly in A. No exact OCR values read from curves. — Figure 7A–B and caption; Results paragraph beginning “To verify further”; Materials and methods: Cell culture and Evaluation of metabolic parameters
Validation of PPARα knockdown: qPCR normalized to GAPDH; Results reports >5-fold, not an exact curve-derived value. — Figure 7A lower histogram and associated Results paragraph
Glial cell comparison shows relative, incomplete selectivity
Cell-based study · LN-229 and U-87MG human glioblastoma cell lines, primary human GBM cells and normal human astrocytes (NHA) [2]
After fenofibrate exposure, glioblastoma models showed greater cell death than NHA, but NHA were not unaffected. Acute respiration inhibition also occurred in every tested cell type.
Literature-Reported Treatment Conditions
- Treatment concentration
- 25 or 50 μM fenofibrate for cell-death comparison; 50 μM for acute respiration traces
- Exposure duration
- 72 h for cell death; separate acute OCR monitoring
- Method
- Flow cytometry using 7-AAD positivity; accompanying extracellular flux measurements
- Vehicle
- DMSO controls in corresponding growth media; DMSO in XF medium for acute OCR
- Reported limits
- The primary-cell comparison does not establish population-wide human response or clinical selectivity. Replicate n is assay replication, not a number of patients.
Methods and source locations
Compound reported in the paper: Fenofibrate; Compound label in the paper: FF
Evidence applies to the paper’s tested fenofibrate material and models; no equivalence to a particular Adooq lot is established.
Figure 9A–E and caption; Results: Glioblastoma cells and normal astrocytes differ in sensitivity to FF; Materials and methods: Cell culture, metabolic parameters and cell death assay
7-AAD-positive cell death after 50 μM fenofibrate for 72 h: Percentages from Results text; Figure 9E caption: average values from three experiments performed in triplicate (n=9). No exact error values or vehicle-adjusted changes inferred. — Figure 9E and caption; corresponding glial sensitivity Results paragraph
Acute OCR across normal and malignant glial models: Mean ± SD; three experiments in triplicate (n=9); no absolute OCR values inferred. — Figure 9A–D and caption; glial sensitivity Results paragraph
