CF3DODA-Me induces apoptosis, degrades Sp1, and blocks the transformation phase of the blebbishield emergency program

• DOI: 10.1007/s10495-017-1359-1
• Publication Date: 2017-03-11T01:09:40Z
• Authors: Rikiya Taoka; Goodwin G. Jinesh; Wenrui Xue; Stephen Safe; Ashish M. Kamat
• Keywords: Vascular Endothelial Growth Factor A; 0303 health sciences; Hydrocarbons, Fluorinated; Caspase 3; Sp1 Transcription Factor; Ribosomal Protein S6 Kinases, 70-kDa; Apoptosis; Vascular Endothelial Growth Factor Receptor-2; Triterpenes; 3. Good health; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Cell Transformation, Neoplastic; Cell Line, Tumor; Neoplastic Stem Cells; Glycyrrhetinic Acid; Humans; Reactive Oxygen Species

Cancer stem cells are capable of undergoing cellular transformation after commencement of apoptosis through the blebbishield emergency program in a VEGF-VEGFR2-dependent manner. Development of therapeutics targeting the blebbishield emergency program would thus be important in cancer therapy. Specificity protein 1 (Sp1) orchestrates the transcription of both VEGF and VEGFR2; hence, Sp1 could act as a therapeutic target. Here, we demonstrate that CF3DODA-Me induced apoptosis, degraded Sp1, inhibited the expression of multiple drivers of the blebbishield emergency program such as VEGFR2, p70S6K, and N-Myc through activation of caspase-3, inhibited reactive oxygen species; and inhibited K-Ras activation to abolish transformation from blebbishields as well as transformation in soft agar. These findings confirm CF3DODA-Me as a potential therapeutic candidate that can induce apoptosis and block transformation from blebbishields.