Abstract
Selenium is an essential trace element and has shown chemopreventive or therapeutic activities on human solid cancers; however, whether it has anticancer effects on leukemia has not yet been elucidated. The present study was designed to determine the role of selenium on HL-60 human promyelocytic leukemia cells. We found that 100 nM of sodium selenite (Se) had no significant effects on cell proliferation, apoptosis and the cell cycle; however, a higher concentration of 250 nM of Se significantly inhibited cell proliferation, promoted apoptosis and induced cell cycle arrest at the S phase after 48 h of treatment (P<0.05), thus demonstrating the anticancer activities of selenium in leukemia. However, the decrease in c-Jun NH2-terminal kinase 1 (JNK1) expression by targeting JNK1 using small interfering RNA attenuated the inhibitory effects of Se on cell proliferation and the induction of apoptosis. Mechanistic studies showed that the anticancer activities of Se were associated with the enhanced phosphorylation of JNK1 and the increased expression of the cell cycle regulators, p21 and p27, as well as the downregulation of cyclin D1. Our data provide further evidence that the appropriate concentration of selenium has therapeutic potential in leukemia.
Highlights
Leukemia is one of the most comment malignant diseases worldwide
In the present study, using HL-60 human promyelocytic leukemia cells, we found that a higher concentration of selenium significantly inhibited cell proliferation, induced apoptosis, as well as changes in the cell cycle, which were associasted with the enhanced phosphorylation of JNK and the increased expression of p21 and p27, and with the deceased expression of cyclin D1
We found that the knockdown of Jun NH2-terminal kinase 1 (JNK1) abrogated the inhibitory effects of Se on cell proliferation (Fig. 4A) and the induction of apoptosis (Fig. 4B)
Summary
Leukemia is one of the most comment malignant diseases worldwide. Epidemiological studies have shown that in the United States, among males aged >40 years, leukemia is the most common fatal cancer; among females, leukemia is the leading cause of cancer-related mortality before the age of 20. In children (newborns to 14 years of age) almost one third of cancer cases are diagnosed are leukemia ( acute lymphocytic leukemia) [1]. Chemotherapy remains the major strategy for the treatment of leukemia; traditional therapy has lower efficacy and severe side-effects. It is urgent to develop an alternative medicine or alternative therapeutic approaches for the treatment of leukemia. It has been demonstrated that the trace element, selenium, has potential effects on leukemia [2]
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