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
  • Shin, Jae-Sik
  • Woo, Sang Hyeok
  • Lee, Hyung-Chahn
  • Hong, Seung-Woo
  • Yoo, Doo-Hyun
  • 외 7명
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초록

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.

키워드

doxorubicinlow dose of radiationsenescenceErk1/2p38HUMAN TUMOR-CELLSTERMINAL PROLIFERATION ARRESTLACKING FUNCTIONAL P53NF-KAPPA-BLIFE-SPANIN-VITROREPLICATIVE SENESCENCEARTICULAR CHONDROCYTESGAMMA-IRRADIATIONGROWTH ARREST
제목
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
저자
Shin, Jae-SikWoo, Sang HyeokLee, Hyung-ChahnHong, Seung-WooYoo, Doo-HyunHong, Seok-IlLee, Wang-JaeLee, Myeong-SokJin, Young-WooAn, SungkwanJin, Dong-HoonPark, In-Chul
DOI
10.3892/ijo_00000630
발행일
2010-06
유형
Article
저널명
International Journal of Oncology
36
6
페이지
1445 ~ 1452