Vitamin C inhibits p53-induced replicative senescence through suppression of ROS production and p38 MAPK activity

Kim,Jee-Eun; Jin,Dong-Hoon; Lee,Soon-Duck; Hong,Seung-Woo; Shin,Jae-Sik; Lee,Seung-Koo; Jung,Da-Jung; Kang,Jae-Seung; Lee,Wang-Jae

doi:10.3892/ijmm_00000068

November 2008 Volume 22 Issue 5

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November 2008 Volume 22 Issue 5

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Article

Vitamin C inhibits p53-induced replicative senescence through suppression of ROS production and p38 MAPK activity

Authors:
- Jee-Eun Kim
- Dong-Hoon Jin
- Soon-Duck Lee
- Seung-Woo Hong
- Jae-Sik Shin
- Seung-Koo Lee
- Da-Jung Jung
- Jae-Seung Kang
- Wang-Jae Lee
View Affiliations / Copyright

Affiliations: Department of Anatomy and Tumor Immunity Medical Research Center, Seoul National University College of Medicine, Jongno-Gu, Seoul, Korea
Pages: 651-655
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Published online on: November 1, 2008

https://doi.org/10.3892/ijmm_00000068
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Abstract

We previously reported that tumor cells expressing p53 increase intracellular levels of reactive oxygen species (ROS). In this study, we described an inhibitory effect of vitamin C on replicative senescence. Vitamin C was found to inhibit p53-induced senescence in human bladder cancer EJ cells. The senescence-like phenotype (SLP) induced by p53, which showed a morphological change and an irreversible cell cycle arrest, was not observed in vitamin C-treated EJ cells. In addition, vitamin C did not significantly affect normal cell proliferation. We investigated the molecular mechanisms of the inhibitory effect of vitamin C on the development of replicative senescence in EJ cells. We found that vitamin C inhibited this p53-induced ROS generation. Moreover, p38 kinase which was activated during p53-induced senescence was not observed in vitamin C-treated EJ cells. SB203580, a chemical inhibitor of p38 kinase, was found to consistently inhibit p53-induced senescence. Therefore, it is suggested that vitamin C inhibits p53-induced senescence by preventing ROS generation, which in turn leads to the activation of p38 MAPKinase. These results reveal the inhibitory mechanism of vitamin C on cellular senescence.

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Vitamin C inhibits p53-induced replicative senescence through suppression of ROS production and p38 MAPK activity

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