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University of Tennessee, Knoxville

Theses/Dissertations

2009

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Histone Deacetylase Inhibitors For Selective Anti-Cancer Therapeutics, Shambhunath Choudhary Aug 2009

Histone Deacetylase Inhibitors For Selective Anti-Cancer Therapeutics, Shambhunath Choudhary

Doctoral Dissertations

Activating mutations of ras genes are frequently found in human cancers. Since Ras proteins and their functions play an important role in tumorigenesis, it is important to develop targeted anticancer therapeutics against Ras-related human cancers. We observed that in addition to tumorigenic ability, oncogenic H-Ras possesses a novel proapoptotic ability to facilitate the induction of apoptosis by histone deacetylase inhibitors (HDACIs), such as FR901228 and trichostatin A (TSA). HDACIs make up a new class of structurally diverse anticancer agents and have been shown to exhibit antimetastatic and antiangiogenic activities toward malignantly transformed cells. We detected that expression of oncogenic H-Ras …