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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

Authors
Shin, Jae-SikWoo, Sang HyeokLee, Hyung-ChahnHong, Seung-WooYoo, Doo-HyunHong, Seok-IlLee, Wang-JaeLee, Myeong-SokJin, Young-WooAn, SungkwanJin, Dong-HoonPark, In-Chul
Issue Date
Jun-2010
Publisher
SPANDIDOS PUBL LTD
Keywords
doxorubicin; low dose of radiation; senescence; Erk1/2; p38
Citation
INTERNATIONAL JOURNAL OF ONCOLOGY, v.36, no.6, pp.1445 - 1452
Journal Title
INTERNATIONAL JOURNAL OF ONCOLOGY
Volume
36
Number
6
Start Page
1445
End Page
1452
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/13203
DOI
10.3892/ijo_00000630
ISSN
1019-6439
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.
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