Premium
Vitamin C inhibits p53‐induced senescence by preventing ROS generation and p38 MAPKinase activation
Author(s) -
Kim Jee Eun,
Jin Dong Hoon,
Hong Seung Woo,
Shin Jae Sik,
Jung Da Jung,
Lee Seung Koo,
Kang Jae Seung,
Hwang Young Il,
Shin Dong Hoon,
Lee Wang Jae
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.631
Subject(s) - senescence , ascorbic acid , reactive oxygen species , p38 mitogen activated protein kinases , microbiology and biotechnology , intracellular , chemistry , vitamin c , kinase , biology , biochemistry , protein kinase a , food science
We previously reported that tumor cells expressing p53 increase intracellular levels of reactive oxygen species (ROS). In this study, we describe the inhibitory effect of L‐ascorbate (Vitamin C) on replicative senescence induced by a transient p53 over‐expression system using adenovirus vector in EJ human bladder carcinoma cells, lacking a functional p53. As a result, L‐ascorbate was found to inhibit p53‐induced senescence in human bladder cancer EJ cells. Moreover, the senescence‐like phenotype (SLP) induced by p53, which is morphological changes, and irreversible cell cycle arrest, was not observed in L‐ascorbate‐treated EJ cells. On the contrary, ascorbic acid did not significantly affect normal cell proliferation. We investigated the molecular mechanisms of the inhibitory effect of L‐ascorbate on the development of replicative senescence in EJ cells. We found that L‐ascorbate inhibit this p53‐induced ROS generation. Moreover, p38 kinase activated during p53‐induced senescence was not observed in L‐ascorbate‐treated EJ cells. Consistently, a chemical inhibitor of p38 kinase, SB203580 was found to inhibit p53‐induced senescence. Therefore, L‐ascorbate 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 L‐ascorbate on cellular senescence.