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p53‐mediated enhancement of radiosensitivity by selenophosphate synthetase 1 overexpression
Author(s) -
Chung Hyun Ju,
Yoon Sun Il,
Shin Sun Hye,
Koh Yeon A.,
Lee SuJae,
Lee YunSil,
Bae Sangwoo
Publication year - 2006
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20714
Subject(s) - radiosensitivity , gene knockdown , viability assay , downregulation and upregulation , cancer cell , ionizing radiation , reactive oxygen species , cell culture , gene silencing , cell , biology , chemistry , cancer research , microbiology and biotechnology , cancer , biochemistry , medicine , irradiation , radiation therapy , gene , genetics , physics , nuclear physics
Selenium has been associated with cancer prevention. Despite vast knowledge of selenium effect on various health conditions, functional characterization of selenium metabolic enzymes on cellular physiology has been limited. Therefore, to gain insight into the mechanisms underlying cancer prevention by selenium, we investigated sps1 , one of the two human selenophosphate synthetase genes for its role in cancer cell's response to ionizing radiation. Although stable expression of Sps1 protein per se had little effect on cell proliferation, concurrent irradiation decreased viability of the sps1 cell line. The increased sensitivity of the cell lines to ionizing radiation was correlated with increased p53 activity as well as with simultaneous up‐ and downregulation of Bax and Bcl2, respectively. Knockdown of sps1 and p53 by small interfering RNA method revealed that the level of p53 was proportional to that of Sps1 and that the increased radiosensitivity was dependent upon p53. Sps1 cell lines displayed decreased level of reactive oxygen species (ROS) with concomitant increase of certain redox enzymes. Furthermore, p53 activity was regulated by cellular redox via Ref1 in sps1 cell lines. Collectively, our results demonstrated that sps1 was able to affect cell viability upon ionizing radiation via modulation of p53 activity. They further suggest that Sps1 and its reaction product selenophosphate might be involved in cancer prevention in a p53‐dependent manner and could be applied to development of a novel cancer therapy. J. Cell. Physiol. 209: 131–141, 2006. © 2006 Wiley‐Liss, Inc.