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

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Abstract

Purpose

Propranolol, a non-selective β-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 β-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 propranolol-induced 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-ΚB pathway were examined by qRT-PCR array.

Results

IC50 values of propranolol on U266 cells were calculated as 141, 100, and 75 μM 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, NF-κB, and the inhibitors of NF-κB 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.

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Acknowledgments

We thank Biotechnology and Bioengineering Center staff of Izmir Institute of Technology for their help and technical support. This study was supported by the Turkish Academy of Sciences Outstanding Young Investigator Programme.

Conflict of interest

We, the authors of the manuscript, do not have any conflict of interest.

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Authors and Affiliations

  1. Bone Marrow Transplantation Unit, Faculty of Medicine, Adana Teaching and Medical Research Center, Baskent University, Adana, Turkey

    Hakan Ozdogu

  2. Adana Adult Bone Marrow Center, Cell Processing Unit, Baskent University, Ankara, Turkey

    Ilknur Kozanoglu

  3. Department of Molecular Biology and Genetics, Izmir Institute of Technology, 35430, Urla, Izmir, Turkey

    Melis Kartal Yandim & Yusuf Baran

  4. Department of Molecular Medicine, Institute of Experimental Medical Research, Istanbul University, Capa, Istanbul, Turkey

    Zeynep Birsu Cincin & Bedia Cakmakoglu

  5. Faculty of Medicine, Department of Physiology, Baskent University, Ankara, Turkey

    Ilknur Kozanoglu

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  1. Ilknur Kozanoglu
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  2. Melis Kartal Yandim
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  3. Zeynep Birsu Cincin
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  4. Hakan Ozdogu
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Correspondence to Yusuf Baran.

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Kozanoglu, I., Yandim, M.K., Cincin, Z.B. et al. New indication for therapeutic potential of an old well-known drug (propranolol) for multiple myeloma. J Cancer Res Clin Oncol 139, 327–335 (2013). https://doi.org/10.1007/s00432-012-1331-y

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  • DOI: https://doi.org/10.1007/s00432-012-1331-y

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