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Title: New indication for therapeutic potential of an old well-known drug (propranolol) for multiple myeloma
Authors: Kozanoğlu, İlknur
Kartal Yandım, Melis
Çinçin, Zeynep Birsu
Özdoğu, Hakan
Çakmakoğlu, Bedia
Baran, Yusuf
Keywords: Apoptosis
Multiple myeloma
NF-κB pathway
Drug cytotoxicity
Publisher: Springer Verlag
Source: Kozanoğlu, I., Kartal Yandım, M., Çinçin, Z.B., Özdoğu, H., Çakmakoğlu, B., and Baran, Y. (2013). New indication for therapeutic potential of an old well-known drug (propranolol) for multiple myeloma. Journal of Cancer Research and Clinical Oncology, 139(2), 327-335. doi:10.1007/s00432-012-1331-y
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.
ISSN: 0171-5216
Appears in Collections:Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection

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