Identification of a Novel Synthetic Thiazolidin Compound Capable of Inducing c-Jun NH2-Terminal Kinase–Dependent Apoptosis in Human Colon Cancer Cells

摘要: Development of new therapeutic agents for colon cancer is highly desirable. To this end, we screened a chemical library anticancer and identified synthetic compound, 5-(2,4-dihydroxybenzylidene)-2-(phenylimino)-1,3-thiazolidin (DBPT), which kills cells more effectively than it normal human fibroblasts. The molecular mechanism the antitumor action DBPT was further analyzed in three colorectal cell lines. inhibited growth cells, independent p53 P-glycoprotein status, whereas fibroblasts were unaffected at same IC50. Over time, DLD-1 treated with underwent apoptosis. general caspase inhibitor benzyloxycarbonyl-valine-alanine-aspartate-fluoromethylketone partially blocked DBPT-induced apoptosis dose-dependent manner. apoptosis, including cytochrome c release activation, abrogated when c-Jun NH2-terminal kinase (JNK) activation either specific JNK or dominant-negative JNK1 gene. However, constitutive alone did not replicate effects excessive by adenovirus encoding MKK7 had little influence on Our results suggested that induces lines through caspase-dependent caspase-independent pathways crucial its analogues might be useful as agents.