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Low doses of ionizing radiation suppress doxorubicin-induced senescence-like phenotypes by activation of ERK1/2 and suppression of p38 kinase in MCF7 human breast cancer cells

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Authors
Shin, Jae-Sik; Woo, Sang Hyeok; Lee, Hyung-Chahn; Hong, Seung-Woo; Hong, Seok-Il; Lee, Myeong-Sok; An, Sungkwan; Park, In-Chul; Jin, Dong-Hoon; Jin, Young-Woo; Lee, Wang-Jae; Yoo, Doo-Hyun
Issue Date
2010-06
Publisher
SPANDIDOS PUBL LTD
Citation
INTERNATIONAL JOURNAL OF ONCOLOGY; Vol.36, No.6; 1445-1452
Keywords
doxorubicinsenescencelow dose of radiationErk1/2p38
Abstract
Low-dose radiation has a variety of effects on cellular activities, including the cell division cycle, apoptosis, proliferation and senescence. However, the effects of low doses of radiation remain controversial. In this study, we examined the effects of low-dose radiation on cellular senescence. We treated MCF7 cells with 0.01 mu g/ml doxorubicin to induce replicative senescence, 2 h after exposure to low doses of ionizing radiation of 0.05, 0.1, or 0.2 Gy. The status of p53, senescence-associated beta-galactosidase activity, p38 kinase levels, H2AX levels and ERK/MAPK levels were examined. Low doses of ionizing radiation inhibit doxorubicin-induced senescence in human breast cancer MCF7 cells. The phosphorylations of both p38 MAP kinase and p53 induced by doxorubicin were suppressed by low doses of ionizing radiation. The senescence was inhibited without genomic damage, because the level of gamma-H2AX protein was not changed. Moreover, low doses of ionizing radiation inhibited senescence through the activation of ERK1/2. The results thus suggest that low doses of radiation suppress doxorubicin-induced replicative senescence through the inhibition of p38-dependent phosphorylation of p53 and by activation of ERK1/2, without genomic damage. Overall, our results suggest that low doses of ionizing radiation may have a protective role against replicative senescence induced by doxorubicin.
ISSN
1019-6439
Language
English
URI
http://hdl.handle.net/10371/78661
DOI
https://doi.org/10.3892/ijo_00000630
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College of Medicine/School of Medicine (의과대학/대학원)Anatomy (해부학전공)Journal Papers (저널논문_해부학전공)
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