1. Erythropoietin (EPO) can reverse radiotherapy-induced anaemia by stimulating bone marrow cells to produce erythrocytes. However, there are limited studies that address the mechanisms by which EPO exerts its beneficial effects in radiotherapy-induced anaemia. In the present study, we used a human bone marrow-derived EPO-dependent leukaemia cell line UT-7/EPO that progressed further in erythroid development to evaluate the anti-apoptotic effects of EPO on irradiated human erythroid progenitor. 2. The UT-7/EPO cells exposed to gamma-irradiation were cultured in the presence or absence of EPO at a concentration of 7 U/mL. The cell viability, cell apoptosis and the expression of apoptosis-related proteins Bcl-2, Bax and caspase 3 were examined. 3. The results showed that EPO protected the viability of human UT-7/EPO cells exposed to gamma-irradiation. EPO significantly inhibited gamma-irradiation-induced apoptosis in human UT-7/EPO cells: a significant decrease in the percentage of apoptotic cells was observed (62, 69 and 62% at 24, 48 and 72 h, respectively). Furthermore, EPO significantly increased the expression of Bcl-2 protein and the relative Bcl-2/Bax ratio, and decreased the activation of caspase 3 and formation of the p17 and p12 cleavage in similar conditions. 4. In conclusion, EPO exerts anti-apoptotic effects on irradiated human UT-7/EPO cells through upregulation of Bcl-2 protein and the relative Bcl-2/Bax ratio, and by decreasing the activation of caspase 3. These findings may contribute to our understanding of the beneficial function of EPO in radiotherapy-induced anaemia.
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http://dx.doi.org/10.1111/j.1440-1681.2010.05370.x | DOI Listing |
Int J Oncol
February 2018
Division of Pulmonology, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria.
Lung cancer patients have the highest incidence of anemia among patients with solid tumors. The use of recombinant human erythropoietin (Epo) has consistently been shown to reduce the need for blood transfusions and to increase hemoglobin levels in lung cancer patients with chemotherapy-induced anemia. However, clinical and preclinical studies have prompted concerns that Epo and the presence of its receptor, EpoR, in tumor cells may be responsible for adverse effects and, eventually, death.
View Article and Find Full Text PDFJ Interferon Cytokine Res
May 2016
Cytokines and Growth Factors Section, Biotherapeutics Group, National Institute for Biological Standards and Control, Potters Bar, United Kingdom .
IL-27 is a pleiotropic cytokine of the IL-6/IL-12 family with diverse biological functions. Previous in vivo studies have suggested the antitumor activities of IL-27 in animal models, whereas clinical observations indicate the link of IL-27 in tumor progression. IL-27 has recently been shown to cause inhibition of proliferation on primary leukemic cells from pediatric patients, but information on its role in human leukemic cell lines is limited.
View Article and Find Full Text PDFMol Pharmacol
August 2015
Laboratory of Pharmacoimmunology, Integrated Research Institute of Pharmaceutical Sciences, College of Pharmacy, Catholic University of Korea, Bucheon, Republic of Korea (J.-G.O., H.E.K., T.-H.H.); College of Pharmacy, Dongguk University-Seoul, Seoul, Republic of Korea (Y.-W.C.); Department of Biotechnology, Hoseo University, Baebang, Asan, Chungnam, Republic of Korea (S.-J.K.); and College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea (J.M.C., S.K.K.)
Although ingenol 3,20-dibenzoate (IDB) is known as a selective novel protein kinase C (PKC) agonist, its biologic actions and underlying mechanisms remain incompletely understood. In this study, we identified IDB as a proliferative agent for an erythropoietin (EPO)-dependent cell line, UT-7/EPO, through the screening of a natural compound library. To clarify the underlying mechanism of IDB's EPO-like activities, we thoroughly analyzed the mutual relation between EPO and IDB in terms of in vitro and in vivo activities, signaling molecules, and a cellular receptor.
View Article and Find Full Text PDFPLoS One
March 2016
Integrative Bioscience and Biomedical Engineering, Graduate School of Advanced Science and Engineering, Waseda University, Center for Advanced Biomedical Science, TWIns building, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan; Department of Biology, School of Education, Waseda University, Center for Advanced Biomedical Science, TWIns building, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.
Erythropoietin (EPO), the primary regulator of erythropoiesis, is a heavily glycosylated protein found in humans and several other mammals. Intriguingly, we have previously found that EPO in Xenopus laevis (xlEPO) has no N-glycosylation sites, and cross-reacts with the human EPO (huEPO) receptor despite low homology with huEPO. In this study, we introduced N-glycosylation sites into wild-type xlEPO at the positions homologous to those in huEPO, and tested whether the glycosylated mutein retained its biological activity.
View Article and Find Full Text PDFExp Hematol
May 2015
Division of Molecular and Clinical Genetics, Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan; Department of Advanced Molecular and Cell Therapy, Kyushu University Hospital, Fukuoka, Japan. Electronic address:
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