|ZHAI, CHANGHUI - Jilin University|
|WU, RYAN T.Y. - University Of Maryland|
|CHENG, WEN-HSING - Mississippi State University|
Submitted to: PLoS One
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/25/2016
Publication Date: 7/12/2016
Publication URL: http://handle.nal.usda.gov/10113/63159
Citation: Zhai, C., Wu, R., Zeng, H., Cheng, W. 2016. Loss of selenium-binding protein 1 decreases sensitivity to clastogens and intracellular selenium content in HeLa cells. PLoS One. 11(7):e0158650. doi:10.1371/journal.pone.01586.
Interpretive Summary: Epidemiological evidence indicates that selenium, an essential nutrient (trace element), is inversely associated with cancer risk. It has been reported that the selenium-binding protein 1 (SBP1) tightly interacts with selenium, and loss of SBP1 expression is frequently observed in many cancers. However, the consequence of SBP1 loss is not well understood. In this study, we asked whether the loss of SBP1 could modulate the response when cancer cells were under stress (e., g., reactive oxygen species or DNA-damaging agents). We found that SBP1 increases both the sensitivity of cancer cells to the stress signaling (e.g., reactive oxygen species) and the retention of intracellular selenium (an essential nutrient). This finding suggests a new cancer treatment strategy by selenium delivery through SBP1 may be of clinical potential as a complementary approach to current strategy treating cancer. The information will be useful for scientists and health-care professionals who are interested in using selenium as a nutrient and cancer prevention.
Technical Abstract: Selenium-binding protein 1 (SBP1) is not a selenoprotein but structurally binds selenium. Loss of SBP1 during carcinogenesis usually predicts poor prognosis. Because genome instability is a hallmark of cancer, we hypothesized that loss of SBP1 modulates cellular selenium content and the response of cancer cells to DNA-damaging agents. To test this hypothesis, we knocked down SBP1 expression in HeLa cells by employing a short hairpin RNA (shRNA) approach. Knockdown of SBP1 resulted in reduced sensitivity to cellular exposure to hydrogen peroxide, paraquat and camptothecin, levels of reactive oxidative species after hydrogen peroxide treatment, and retention of intracellular selenium content after selenomethionine treatment in HeLa cells. Results from Western analyses showed that treatment of HeLa cells with selenomethionine resulted in increased SBP1 protein expression in a dose-dependent manner. The migration potential of HeLa cells with SBP1 knockdown was greater than that of control cells with scrambled shRNA. Altogether, SBP1 promotes the sensitivity of HeLa cells to clastogens in association with intracellular selenium retention and retarded cell migration, suggesting a new cancer treatment strategy by selenium delivery through SBP1.