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

• Published in: International journal of oncology Vol. 36; no. 6; pp. 1445 - 1452
• Main Authors: SHIN, Jae-Sik, SANG HYEOK WOO, JIN, Dong-Hoon, PARK, In-Chul, LEE, Hyung-Chahn, HONG, Seung-Woo, YOO, Doo-Hyun, HONG, Seok-Il, LEE, Wang-Jae, LEE, Myeong-Sok, JIN, Young-Woo, AN, Sungkwan
• Format: Journal Article
• Language: English
• Published: Athens Editorial Academy of the International Journal of Oncology 01.06.2010
• Subjects: Antibiotics, Antineoplastic - pharmacology; Biological and medical sciences; Blotting, Western; Breast Neoplasms - metabolism; Cell Line, Tumor; Cellular Senescence - drug effects; Cellular Senescence - radiation effects; DNA Damage - drug effects; DNA Damage - radiation effects; Doxorubicin - pharmacology; Enzyme Activation - drug effects; Enzyme Activation - radiation effects; Extracellular Signal-Regulated MAP Kinases - drug effects; Extracellular Signal-Regulated MAP Kinases - radiation effects; Female; Gynecology. Andrology. Obstetrics; Histones - drug effects; Histones - radiation effects; Humans; Mammary gland diseases; Medical sciences; p38 Mitogen-Activated Protein Kinases - drug effects; p38 Mitogen-Activated Protein Kinases - radiation effects; Phenotype; Phosphorylation; Radiation, Ionizing; Tumor Suppressor Protein p53 - drug effects; Tumor Suppressor Protein p53 - radiation effects; Tumors; Antineoplastic agent; Senescence; Breast disease; Doxorubicin; Ionizing radiation; Extracellular signal-regulated protein kinase 2; Isomerases; Cancerology; p38; Extracellular signal-regulated protein kinase 1; Tumor cell; Human; DNA topoisomerase (ATP-hydrolysing); Enzyme; Transferases; Low dose; Erkl/2; Enzyme inhibitor; Mitogen-activated protein kinase; Breast cancer; Topoisomerase II inhibitor; Malignant tumor; Mammary gland diseases; Radiation dose; Phenotype; Kinase; low dose of radiation; Anthracyclins; Cancer
• ISSN: 1019-6439; 1791-2423
• DOI: 10.3892/ijo_00000630

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.