New indication for therapeutic potential of an old well-known drug (propranolol) for multiple myeloma

Abstract

Purpose Propranolol, a non-selective b-adrenergic receptor blocker, has been used for the treatment of the patients with hypertension for more than 50 years. There are several in vitro and in vivo evidences that b-adrenergic receptor antagonists inhibit proliferation and angiogenesis and also increase apoptosis in breast, skin, and colon cancers. The aim of this study was to investigate the cytotoxic and apoptotic effects of propranolol and the genes involved in propranololinduced apoptosis in multiple myeloma cells. Methods Time-dependent antiproliferation and apoptotic effects of propranolol were subsequently determined by MTT cell proliferation assay, changes in caspase-3 activity, loss of mitochondrial membrane potential (MMP), and also the localization of phosphatidylserine in the plasma membrane. Changes in expression levels of NF-JB pathway were examined by qRT-PCR array.Results IC50 values of propranolol on U266 cells were calculated as 141, 100, and 75 lM after 24-, 48-, and 72-h propranolol exposure, respectively. There were significant increases in caspase-3 activity, loss of MMP, and increases in apoptotic cell population in response to propranolol in U266 cells in a time-and dose-dependent manner. There were increases in expression levels of BCL10, TRAF family members, interleukins, TLR1-4, TNFRSF10B, NFjB, and the inhibitors of NF-jB genes, and significant decreases in expression levels of Bcl-2 in response to propranolol treatment were observed. Conclusion These results revealed that propranolol has antiproliferative and apoptotic effects on multiple myeloma cells. Being supported with in vivo analyses, propranolol can be a good and economical way to treat multiple myeloma patients.

Epinephrine Stimulates Cell Proliferation and Induces Chemoresistance in Myeloma Cells through the β-Adrenoreceptor in vitro

“…The adverse effects of propranolol are mild and manageable with long-term use [14]. Although an antimyeloma effect was first reported last year [11], the antitumor effect is consistent with results obtained with other solid-tumor models including breast cancer, acute leukemia, neuroblastoma, etc. [4,10,15,16].…”

“…Until now, there are only a few reports on the effect of catecholamine and the β-receptor on MM cells. Only one research group found that propranolol, a nonspecific β-receptor antagonist, inhibits myeloma cell proliferation and induces cell apoptosis in vitro [11]. …”

Metformin and propranolol combination prevents cancer progression and metastasis in different breast cancer models

“…We contributed to highlight the drug deleterious effects on mitochondrial network functions and dynamics in various cancer cells [44, 45], but Prop mechanism of action remained non-elucidated in breast cancer cells. Here, we showed that Prop induces apoptosis in various breast cancer cell lines.…”

Repurposing Drugs in Oncology (ReDO)—Propranolol as an anti-cancer agent

“…Kozanoglu et al investigated the in vitro effect of PRO on the U266 human multiple myeloma cell line [70]. They showed a dose and time dependent effect on cell proliferation and apoptosis, with IC50 values of 141, 100, and 75 μM after 24-, 48-, and 72-h PRO exposure, respectively.…”