A new tellurium-containing amphiphilic molecule induces apoptosis in HCT116 colon cancer cells

• Published in: Biochimica et biophysica acta Vol. 1840; no. 6; pp. 1808 - 1816
• Main Authors: Du, Peng, Saidu, Nathaniel Edward Bennett, Intemann, Johanna, Jacob, Claus, Montenarh, Mathias
• Format: Journal Article
• Language: English
• Published: Netherlands 01.06.2014
• Subjects: antineoplastic agents; Antineoplastic Agents - pharmacology; apoptosis; Apoptosis - drug effects; cell cycle; Cell Cycle Checkpoints - drug effects; colorectal neoplasms; Endoplasmic Reticulum Stress; epithelium; fluorescence; HCT116 Cells; Heme Oxygenase-1 - metabolism; Humans; neoplasm cells; NF-E2-Related Factor 2 - metabolism; oxygen; proteins; selenium; signal transduction; stress response; superoxide anion; Superoxides - metabolism; tellurium; Tellurium - pharmacology; Transcription Factor CHOP - analysis; Transcription Factor CHOP - physiology; Western blotting; Cancer cell; Reactive oxygen species; Endoplasmic reticulum stress pathway; Non-cancer cell; Apoptosis
• ISSN: 0304-4165; 0006-3002
• DOI: 10.1016/j.bbagen.2014.02.003

Chalcogen-based redox modulators over the years have attracted considerable attention as anti-cancer 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 HCT116. 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. With 50μM of DP41, we observed an increase in O2(-) formation. There was, however, no such increase in O2(-) after treatment with the corresponding selenium compound under the same conditions. In the case of DP41, the production of O2(-) radicals was followed by an up-regulation of Nrf2, HO-1, phospho-eIF2α 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 O2(-) radicals nor did they induce the ER signaling pathway or apoptosis. The tellurium-containing compound DP41, in contrast to the corresponding selenium compound, induces O2(-) radical formation and oxidative and ER stress responses, including CHOP activation and finally apoptosis. These results indicate that DP41 is a redox modulating agent with promising anti-cancer potentials.