Abstract
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.
Original language | English (US) |
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Pages (from-to) | 719-729 |
Number of pages | 11 |
Journal | Apoptosis |
Volume | 22 |
Issue number | 5 |
DOIs | |
State | Published - May 1 2017 |
Keywords
- Blebbishields
- Cellular transformation
- K-Ras
- Sp1
- VEGFR2
ASJC Scopus subject areas
- Pharmacology
- Pharmaceutical Science
- Clinical Biochemistry
- Cell Biology
- Biochemistry, medical
- Cancer Research