Leonard Christopher Schmeel1,2, Frederic Carsten Schmeel1,2, Ingo G H Schmidt-Wolf3. 1. Department of Radiology and Radiation Oncology, University Hospital Bonn, Bonn, Germany. 2. Center for Integrated Oncology (CIO), Medical Clinic and Policlinic III, University Hospital Bonn, Bonn, Germany. 3. Center for Integrated Oncology (CIO), Medical Clinic and Policlinic III, University Hospital Bonn, Bonn, Germany Ingo.Schmidt-Wolf@ukbonn.de.
Abstract
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. Copyright
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 murinemyeloma/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. Copyright
Authors: Martial Caillaud; Nipa H Patel; Wisam Toma; Alyssa White; Danielle Thompson; Jared Mann; Tammy H Tran; Jane L Roberts; Justin L Poklis; John W Bigbee; Xianjun Fang; David A Gewirtz; M Imad Damaj Journal: Cancers (Basel) Date: 2020-12-29 Impact factor: 6.639