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In Vitro Apoptosis Induction by Fenofibrate in Lymphoma and Multiple Myeloma
Leonard Christopher Schmeel1,2, Frederic Carsten Schmeel1,2, Ingo G H Schmidt-Wolf3
1Department of Radiology and Radiation Oncology, University Hospital Bonn, Bonn, Germany.
Background/Aim:
Recent innovations in the treatment of multiple myeloma have enriched our therapeutic repertoire regarding the treatment of multiple myeloma during the last decades. However, despite today's therapies many multiple myeloma (MM) patients experience relapse of disease and eventually remain incurable. Wnt/β-catenin signaling has been demonstrated in lymphoma and MM, rendering related signaling molecules promising therapeutic targets. Fenofibrate, an extensively scrutinized and widely used drug for primary hypercholesterolemia or mixed dyslipidemia, has proven anticarcinogenic properties mediated by peroxisome proliferator-activated receptor-alpha (PPARα) agonism, thereby also influencing WNT-associated signaling molecules.
Materials And Methods:
The antitumor apoptotic effect of fenofibrate at doses ranging from 0.1-200 μM was investigated on a total of seven human, two murine myeloma/lymphoma cell lines and two healthy control cell lines, as determined by 3'3-Dihexyloxacarbocyanine iodide (DiOC6) and propidium iodide (PI) staining in flow cytometry.
Results:
Fenofibrate significantly reduced viability due to apoptosis induction in all investigated myeloma and lymphoma cell lines in a dose-dependent manner, whereas healthy control cells were less sensitive.
Conclusion:
Our results provide a rationale for future in vitro and in vivo studies with fenofibrate as a safe and well-tolerated agent in MM and lymphoma treatment.
Insights
Fenofibrate, a cholesterol-lowering drug, effectively induced apoptosis in multiple myeloma and lymphoma cells. This suggests fenofibrate
Area of Science:
- Oncology
- Pharmacology
Background:
- Multiple myeloma (MM) remains a challenge with frequent relapses despite advanced therapies.
- Wnt/β-catenin signaling is implicated in MM and lymphoma, presenting therapeutic targets.
- Fenofibrate, a PPARα agonist, exhibits anticancer properties and influences WNT signaling.
Purpose of the Study:
- To investigate the antitumor effects of fenofibrate on multiple myeloma and lymphoma cell lines.
- To evaluate fenofibrate's impact on cancer cell viability and apoptosis.
Main Methods:
- Tested fenofibrate (0.1-200 μM) on seven human and two murine myeloma/lymphoma cell lines.
- Utilized DiOC6 and propidium iodide staining with flow cytometry to assess apoptosis.
- Compared fenofibrate's effects on cancer cells versus two healthy control cell lines.
Main Results:
- Fenofibrate significantly reduced cancer cell viability across all tested myeloma and lymphoma lines.
- Apoptosis was induced in a dose-dependent manner by fenofibrate.
- Healthy control cells demonstrated lower sensitivity to fenofibrate compared to cancer cells.
Conclusions:
- Fenofibrate demonstrates significant anti-myeloma and anti-lymphoma activity.
- Fenofibrate shows potential as a safe and well-tolerated therapeutic agent for MM and lymphoma.
- Further in vitro and in vivo studies are warranted to explore fenofibrate's clinical utility.
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