Fluoxetine as an antidepressant medicine improves the effects of ionizing radiation for the treatment of glioma
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Fluoxetine as an antidepressant medicine improves the effects of ionizing radiation for the treatment of glioma Seyed Jalal Hosseinimehr 1 & Seydeh Halimeh Najafi 1 & Fatemeh Shafiee 1 & Sodabeh Hassanzadeh 1 & Soghra Farzipour 1 & Arash Ghasemi 2 & Hossein Asgarian-Omran 3,4 Received: 8 March 2020 / Accepted: 30 April 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Radiotherapy is a cancer treatment protocol which delivers high dose of ionizing radiation (IR) to tumor. Tumor resistance and side effects induced by IR still are the major challenges in radiotherapy. The purpose of this study was to evaluate the synergistic killing effect of fluoxetine (FL) with IR on glioma cancer cell (U-87 MG), as well as radioprotective effect of FL against cellular toxicity induced by IR on non-malignant human fibroblast cell (HFFF2). Firstly, the inhibitory effects of FL on cell proliferations were evaluated in U-87 MG and HFFF2 cells. The clonogenic and MTT assays were used to evaluate the radiosensitivity and radioprotective effects of FL on cancer and non-malignant cells. The frequencies of apoptotic cells were evaluated by flow cytometry on both cancer and normal cells. Results showed that FL exhibited anti-cancer effect on glioma cells, while cellular toxicity was low in HFFF2 cells treated with FL. FL decreased the viable colonies and enhanced apoptotic cells when U-87 cells were treated with FL prior irradiation. For comparison, FL exhibited radioprotective effect through increasing cellular proliferation rate and reducing apoptosis in HFFF2 cells against IR. The results showed that FL enhanced the IR-induced glioma cancer cell death and apoptosis, whereas it exhibited a radioprotective effect on normal fibroblast cells suggesting that FL administration may improve glioma radiotherapy. Keywords Fluoxetine . Ionizing radiation . Radiosensitizing . Radioprotective . Glioma . Apoptosis
Introduction Ionizing radiation (IR) is an effective strategy along with surgery and chemotherapy in treatment of cancer. The main mechanism actions of radiotherapy are production of free radicals and inducing oxidative stress into cells. These highly reactive substances are able to react with DNA may result in cellular malfunction and death. However, IR that is produced by a radiotherapy machine, * Seyed Jalal Hosseinimehr [email protected]; [email protected] 1
Department of Radiopharmacy, Faculty of Pharmacy, Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran
2
Department of Radiology and Radiation Oncology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
3
Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
4
Immunogenetics Research Center, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
is concentrating on tumor tissue, radiotherapy has two limitations associated with treating as resistance of cancer cells to IR and side effects on normal tis
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