The animation demonstrates the mechanism of action of Curaxin molecules. Curaxins are candidate anti-cancer treatments developed by Incuron company.
To create Curaxins, Incuron collaborated with the Roswell Park Cancer Institute (RPCI), recognized as “Comprehensive Cancer Center” by the U.S. National Cancer Institute. RCPI’s faculty serve on the U.S. National Comprehensive Cancer Network panels that create the internationally recognized Clinical Practice Guidelines in Oncology.
In 2016 RCPI invited Visual Science to create an animation on Curaxin technology as a part of a larger film about RPCI accomplishments in cancer research field. Visualizing Curaxins’ mechanism of action was a complex task because the scientifically accurate animation of large macromolecular complexes with DNA and proteins requires large computing capacity.
Curaxins are small molecules that have demonstrated the ability to kill a broad range of human tumor cells and sensitize tumor cells to other cancer treatments. Curaxins interfere with normal DNA packaging in the nuclei of the tumor cells, which triggers a number of changes in the biochemical cascades important for the tumor growth leading to the destruction of the cancer cells (1).
Curaxins binding to cellular DNA results in its detachment from histones — special proteins which assemble in nucleosomes, structures that play one of the key roles in DNA compaction in the nucleus (DNA and nucleosomes visualization on the Visual Science “DNA, RNA, Protein” poster). DNA detachment from histones leads to accumulation of negative supercoiling and conversion of multiple regions of genomic DNA into left-handed Z-form instead of right-handed B-form (DNA fragments in A, B and Z forms). It is thought that Z-DNA is then recognized by histone chaperones like FACT, which, in turn, activate a response that involves p53 — one of the most important tumor suppressors in the body (2).
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