MYC Inhibition Through Small Compound Targeting of the NHE III₁ i-Motif
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractCurrent cancer therapies often fail to eradicate a patient's tumors completely due to complications arising from protein mutations, tumor cell migration, and interference with DNA replication. These issues can be circumvented by inhibiting the oncogenes responsible for tumor growth through targeting of secondary non-helical structures present in the oncogenes' promoters. Through screening of NCI compound libraries we have found two compounds, IMC 30 and IMC 31, that are capable of reducing the expression of the oncogene MYC through interaction with the i-motif structure in its promoter region. These compounds are also capable of inducing cell death in cells that are reliant on MYC overexpression for growth. A third compound, IMC 16, was capable of inducing an increase in MYC expression in addition to inducing apoptosis in MYC dependent cells. This result indicates a possibility that increasing the expression of MYC in MYC dependent tumors may cause a shift in its primary function from cell growth to induction of apoptosis. The compounds IMC 30, IMC 31, and IMC 16 will be subjected to further experimentation with more complicated biological systems in an effort to develop them as cancer therapeutics.
Degree ProgramHonors College