In vitro apoptosis induction by fenofibrate in lymphoma and multiple myeloma

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/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 (PPAR) agonism, thereby also influencing WNT-associated signaling moleculeS. Materials and Methods: The antitumor apoptotic effect of fenofibrate at doses ranging from 0.1-200 M 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 dosedependent 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 welltolerated agent in MM and lymphoma treatment.