科研之友
微信
新浪微博
Facebook
分享链接
摘要
Background: Chalcogen-based redox modulators over the years have attracted considerable attention as anticancer agents. New selenium- and tellurium-containing compounds with a polar head group and aryl-groups of various lengths have recently been reported as biologically active in several organisms. In the present study, we used the most active of the tellurium compound DP41, and its selenium counterpart DP31 to investigate their effects on the human cancer cell line HC1%26apos;116. %26lt;br%26gt;Methods: Cells were treated with DP41 or DP31 and the formation of superoxide radicals was determined using dihydroethidium. Cell cycle analysis and apoptosis was determined by cytofluorimetry. Proteins involved in ER signaling and apoptosis were determined by Western blot analysis and fluorescence microscopy. %26lt;br%26gt;Results: With 50 mu M of DP41, we observed an increase in O-2(-) formation. There was, however, no such increase in O-2(-) after treatment with the corresponding selenium compound under the same conditions. In the case of DP41, the production of O-2(-) radicals was followed by an up-regulatiorpof Nrf2, HO-1, phospho-elF2 alpha and ATF4. CHOP was also induced and cells entered apoptosis. Unlike the cancer cells, normal retinal epithelial ARPE-19 cells did not produce elevated levels of O-2(-) radicals nor did they induce the ER signaling pathway or apoptosis. %26lt;br%26gt;Conclusions: The tellurium-containing compound DP41, in contrast to the corresponding selenium compound, induces O-2(-) radical formation and oxidative and ER stress responses, including CHOP activation and finally apoptosis. %26lt;br%26gt;General significance: These results indicate that DP41 is a redox modulating agent with promising anti-cancer potentials.
- 出版日期2014-6
