The disclosure describes methods for inducing apoptosis of a selected group of vertebrate cells in vivo by reducing the level of thiamin in the cells. Included are methods for inducing apoptosis of cancer cells. Also described are compounds and compositions for use in methods of thiamin depletion and treating diseases such as cancer, and methods for identifying thiamin-depleting agents and for preparing pharmaceutical compositions.
RELATED APPLICATIONS
This application claims the benefit of Fulton et al., U.S. Provisional Application 60/052,377, filed Jul. 11, 1997, entitled METHOD OF INDUCING APOPTOSIS BY REDUCING THE LEVEL OF THIAMIN and Fulton et al., U.S. Provisional Application 60/087,526, filed Jun. 1, 1998, entitled METHOD OF INDUCING APOPTOSIS BY REDUCING THE LEVEL OF THIAMIN, which are hereby incorporated by reference in their entireties, including drawings.
Plant tissue specific gene expression by way of repressor-operator complexes, has enabled outcomes including, without limitation, male sterility and engineered plants having root-specific gene expression of relevant proteins to clean environmental pollutants from soil and water. A mercury hyperaccumulation strategy requires that mercuric ion reductase coding sequence is strongly expressed. The actin promoter vector, A2pot, engineered to contain bacterial lac operator sequences, directed strong expression in all plant vegetative organs and tissues. In contrast, the expression from the A2pot construct was restricted primarily to root tissues when a modified bacterial repressor (LacIn) was coexpressed from the light-regulated rubisco small subunit promoter in above-ground tissues. Also provided are analogous repressor operator complexes for selective expression in other plant tissues, for example, to produce male sterile plants.