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.
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 microg/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.
Shin
Jae-Sik
JS
Department of Anatomy and Tumor Immnunity Medical Research Center, Seoul National University College of Medicine, Seoul 110-799, Korea.
Woo
Sang Hyeok
SH
Lee
Hyung-Chahn
HC
Hong
Seung-Woo
SW
Yoo
Doo-Hyun
DH
Hong
Seok-Il
SI
Lee
Wang-Jae
WJ
Lee
Myeong-Sok
MS
Jin
Young-Woo
YW
An
Sungkwan
S
Jin
Dong-Hoon
DH
Park
In-Chul
IC
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000187:drug effects / Q000528:radiation effects*; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D004317:Doxorubicin / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000528:radiation effects*; D005260:Female; D006657:Histones / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D010641:Phenotype; D010766:Phosphorylation; D011839:Radiation, Ionizing; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000528:radiation effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000528:radiation effects*
D000903:Antibiotics, Antineoplastic; C468783:H2AX protein, human; D006657:Histones; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases