Radiation Response of Human Leukemia/Lymphoma Cells was Improved by 7-Geranyloxycoumarin

Objectives Adult T-cell leukemia/lymphoma (ATLL) is a blood neoplasm with specific geographic distribution. Although radiotherapy is a palliative treatment that provides long-term local control, single use of radiation leads to complications for patients. To introduce a novel multimodal approach aga...

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Main Authors: Ramin Bagheri, Fatemeh B. Rassouli, Hamid Gholamhosseinian, Keyhan Ebrahimi, Shakiba Mahdavi, Sajad Goudarzi, Mehrdad Iranshahi, Houshang Rafatpanah, Mohammad Reza Keramati
Format: Article
Language:English
Published: SAGE Publishing 2022-09-01
Series:Dose-Response
Online Access:https://doi.org/10.1177/15593258221124479
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author Ramin Bagheri
Fatemeh B. Rassouli
Hamid Gholamhosseinian
Keyhan Ebrahimi
Shakiba Mahdavi
Sajad Goudarzi
Mehrdad Iranshahi
Houshang Rafatpanah
Mohammad Reza Keramati
author_facet Ramin Bagheri
Fatemeh B. Rassouli
Hamid Gholamhosseinian
Keyhan Ebrahimi
Shakiba Mahdavi
Sajad Goudarzi
Mehrdad Iranshahi
Houshang Rafatpanah
Mohammad Reza Keramati
author_sort Ramin Bagheri
collection DOAJ
description Objectives Adult T-cell leukemia/lymphoma (ATLL) is a blood neoplasm with specific geographic distribution. Although radiotherapy is a palliative treatment that provides long-term local control, single use of radiation leads to complications for patients. To introduce a novel multimodal approach against ATLL, we investigated combinatorial effects of 7-geranyloxycoumarin and radiation in vitro. Methods Viability of MT-2 cells was determined by resazurin assay upon administration of 7-geranyloxycoumarin alone and followed by radiation. Then, apoptosis was detected by annexin V and propidium iodide, and the expression of candidate genes was analyzed by qPCR. Results Findings revealed significant (P<.0001) improvement in radiation effects upon 7-geranyloxycoumarin pretreatment, most notably when cells were pretreated with 5 µg/ml 7-geranyloxycoumarin for 96 h, exposed to 6 Gy radiation and recovered for 48 h. These results were confirmed by flow cytometry, as the percentage of early and late apoptotic cells was increased after combinatorial treatment. In addition, significant (P< .0001) changes in CD44 , c-MYC , cFLIPL , BMI-1 , NF-κB ( Rel A ), and P53 expression was induced by 7-geranyloxycoumarin and radiation. Conclusions Current research indicated, for the first time, that combinatorial use of 7-geranyloxycoumarin and ionizing radiation could be considered as an effective therapeutic modality for ATLL.
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spelling doaj.art-81466198ddaa48d29ab66e230b8addd72022-12-22T04:26:43ZengSAGE PublishingDose-Response1559-32582022-09-012010.1177/15593258221124479Radiation Response of Human Leukemia/Lymphoma Cells was Improved by 7-GeranyloxycoumarinRamin BagheriFatemeh B. RassouliHamid GholamhosseinianKeyhan EbrahimiShakiba MahdaviSajad GoudarziMehrdad IranshahiHoushang RafatpanahMohammad Reza KeramatiObjectives Adult T-cell leukemia/lymphoma (ATLL) is a blood neoplasm with specific geographic distribution. Although radiotherapy is a palliative treatment that provides long-term local control, single use of radiation leads to complications for patients. To introduce a novel multimodal approach against ATLL, we investigated combinatorial effects of 7-geranyloxycoumarin and radiation in vitro. Methods Viability of MT-2 cells was determined by resazurin assay upon administration of 7-geranyloxycoumarin alone and followed by radiation. Then, apoptosis was detected by annexin V and propidium iodide, and the expression of candidate genes was analyzed by qPCR. Results Findings revealed significant (P<.0001) improvement in radiation effects upon 7-geranyloxycoumarin pretreatment, most notably when cells were pretreated with 5 µg/ml 7-geranyloxycoumarin for 96 h, exposed to 6 Gy radiation and recovered for 48 h. These results were confirmed by flow cytometry, as the percentage of early and late apoptotic cells was increased after combinatorial treatment. In addition, significant (P< .0001) changes in CD44 , c-MYC , cFLIPL , BMI-1 , NF-κB ( Rel A ), and P53 expression was induced by 7-geranyloxycoumarin and radiation. Conclusions Current research indicated, for the first time, that combinatorial use of 7-geranyloxycoumarin and ionizing radiation could be considered as an effective therapeutic modality for ATLL.https://doi.org/10.1177/15593258221124479
spellingShingle Ramin Bagheri
Fatemeh B. Rassouli
Hamid Gholamhosseinian
Keyhan Ebrahimi
Shakiba Mahdavi
Sajad Goudarzi
Mehrdad Iranshahi
Houshang Rafatpanah
Mohammad Reza Keramati
Radiation Response of Human Leukemia/Lymphoma Cells was Improved by 7-Geranyloxycoumarin
Dose-Response
title Radiation Response of Human Leukemia/Lymphoma Cells was Improved by 7-Geranyloxycoumarin
title_full Radiation Response of Human Leukemia/Lymphoma Cells was Improved by 7-Geranyloxycoumarin
title_fullStr Radiation Response of Human Leukemia/Lymphoma Cells was Improved by 7-Geranyloxycoumarin
title_full_unstemmed Radiation Response of Human Leukemia/Lymphoma Cells was Improved by 7-Geranyloxycoumarin
title_short Radiation Response of Human Leukemia/Lymphoma Cells was Improved by 7-Geranyloxycoumarin
title_sort radiation response of human leukemia lymphoma cells was improved by 7 geranyloxycoumarin
url https://doi.org/10.1177/15593258221124479
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