Induction of apoptosis by 1,4-phenylenebis(methylene)selenocyanate in cultured human colon cancer cells.
Using a cultured human colon cancer cell line (Col 2), a structurally diverse group of chemopreventive agents was evaluated for their potential to induce apoptosis. As a result, 1,4-phenylenebis(methylene)selenocyanate (p-xylylselenocyanate; p-XSC) was found to be active in this process. p-XSC, a synthetic organoselenium compound, has been shown to inhibit tobacco-specific 4-(methylnitrosoamino)-(3-pyridyl)-1-butanone-induced tumorigenesis in A/J mouse lung, rat tongue carcinogenesis and colon cancer. Known chemopreventive mechanisms include inhibition of DNA methylation, inhibition of thymidine kinase and reduction of oxidative DNA damage. In order to assess apoptosis induction, the cells were exposed to various concentrations of test substances for 48 hours. Enrichment of mono- and oligonucleosomes in the cytoplasm was monitored as an indication of apoptosis using an ELISA kit. As a result, p-XSC caused dose-dependent enrichment of fragmented nucleosomes. In further studies, p-XSC was found to induce DNA laddering in a dose-dependent manner, while apoptotic cells accumulated in a time-dependent manner up to 96 hours. The apoptotic peaks after treatment of p-XSC were also found as confirmed by the flow cytometric analysis of cell cycle distribution. In an additional study, however, p-XSC-mediated apoptosis was not shown to be dependent on p53 expression. Taken together, these results suggest that induction of apoptosis is one possible mechanism for the cancer chemopreventive activity mediated by p-XSC.
Lee
Sang Kook
SK
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, 60612, USA.
Heo
Yoen Hoi
YH
Steele
Vernon E
VE
Pezzuto
John M
JM
D016588:Anticarcinogenic Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects; D016566:Organoselenium Compounds / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D016566:Organoselenium Compounds; D016159:Tumor Suppressor Protein p53; C074153:1,4-phenylenebis(methylene)selenocyanate