{"id":{"repo_id":"vcu","oai_identifier":"oai:scholarscompass.vcu.edu:etd-1952"},"canonical_url":"https://search.dev.ndltd.org/etd/vcu/oai:scholarscompass.vcu.edu:etd-1952","repository":{"repo_id":"vcu","name":"Virginia Commonwealth University","base_url":"https://scholarscompass.vcu.edu/do/oai/"},"display":{"title":"HMG-CoA Reductase Inhibitors Act Synergistically with UCN-01 Through RAS Inhibition","abstract":"The primary objective of this study is to elucidate the mechanism by which the reagent UCN-01 induces apoptosis when administered to leukemia cells along with HmG-CoA reductase inhibitors, mainly the statins. In this study, we demonstrated that exposure of leukemia cell lines to lovastatin (20 uM, 18 hours) and UCN-01 (100 nM, 18 hours) resulted in mitochondria dysfunction, procaspase 3 and 9 cleavage, and PAW degradation along with marked cytochrome C release and apoptosis. Although similar molecular mechanisms have not yet been confirmed in other cancers, our hypothesis holds that enhanced apoptotic effects of UCN-01 are due in part to lovastatin's ability to block formation of geranylgeranylpyrophosphate and farnesylpyrophosphate by interfering with the rate-limiting step of the mevalonate pathway. Geranylgeranylpyrophosphate and farnesylpyrophosphate induce post-translational modifications in RAS that anchor the protein to the cell membrane so that it acts as a signal transducer to the nucleus, promoting cell proliferation.","abstract_html":"The primary objective of this study is to elucidate the mechanism by which the reagent UCN-01 induces apoptosis when administered to leukemia cells along with HmG-CoA reductase inhibitors, mainly the statins. In this study, we demonstrated that exposure of leukemia cell lines to lovastatin (20 uM, 18 hours) and UCN-01 (100 nM, 18 hours) resulted in mitochondria dysfunction, procaspase 3 and 9 cleavage, and PAW degradation along with marked cytochrome C release and apoptosis. Although similar molecular mechanisms have not yet been confirmed in other cancers, our hypothesis holds that enhanced apoptotic effects of UCN-01 are due in part to lovastatin's ability to block formation of geranylgeranylpyrophosphate and farnesylpyrophosphate by interfering with the rate-limiting step of the mevalonate pathway. Geranylgeranylpyrophosphate and farnesylpyrophosphate induce post-translational modifications in RAS that anchor the protein to the cell membrane so that it acts as a signal transducer to the nucleus, promoting cell proliferation.","abstract_has_math":false,"creators":["Khanna, Payal"],"institution":null,"degree_name":"Master of Science","degree_level":"Thesis","degree_discipline":"Biomedical Engineering","degree_department":null,"school":null,"contributors":["Dr. Steven Grant"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2006,"date_issued":"2006-01-01T08:00:00Z","date_published":"2006-01-01T08:00:00Z","updated_at":"2026-07-24T05:54:40Z","subjects":["farnesylpyrophosphate","UCN-01","geranylgeranylpyrophosphate","mitochondria dysfunction","apoptosis","Biomedical Engineering and Bioengineering","Engineering"],"languages":[],"rights":["© The Author"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://scholarscompass.vcu.edu/etd/953"],"render_values":[{"text":"https://scholarscompass.vcu.edu/etd/953","href":"https://scholarscompass.vcu.edu/etd/953","code":true}]}]},"links":{"outbound_url":"https://doi.org/10.25772/MZXX-F811","outbound_label":"DOI","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Dr. Steven Grant"]},{"key":"dc:creator","label":"Author","values":["Khanna, Payal"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2014-07-09T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biomedical Engineering"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["farnesylpyrophosphate","UCN-01","geranylgeranylpyrophosphate","mitochondria dysfunction","apoptosis","Biomedical Engineering and Bioengineering","Engineering"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["© The Author"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://doi.org/10.25772/MZXX-F811","https://scholarscompass.vcu.edu/etd/953"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The primary objective of this study is to elucidate the mechanism by which the reagent UCN-01 induces apoptosis when administered to leukemia cells along with HmG-CoA reductase inhibitors, mainly the statins. In this study, we demonstrated that exposure of leukemia cell lines to lovastatin (20 uM, 18 hours) and UCN-01 (100 nM, 18 hours) resulted in mitochondria dysfunction, procaspase 3 and 9 cleavage, and PAW degradation along with marked cytochrome C release and apoptosis. Although similar molecular mechanisms have not yet been confirmed in other cancers, our hypothesis holds that enhanced apoptotic effects of UCN-01 are due in part to lovastatin's ability to block formation of geranylgeranylpyrophosphate and farnesylpyrophosphate by interfering with the rate-limiting step of the mevalonate pathway. Geranylgeranylpyrophosphate and farnesylpyrophosphate induce post-translational modifications in RAS that anchor the protein to the cell membrane so that it acts as a signal transducer to the nucleus, promoting cell proliferation."]},{"key":"dc:title","label":"Title","values":["HMG-CoA Reductase Inhibitors Act Synergistically with UCN-01 Through RAS Inhibition"]}]}],"canonical_facts":{"dc:contributor":["Dr. Steven Grant"],"dc:creator":["Khanna, Payal"],"dc:date.available":["2014-07-09T07:00:00Z"],"dc:description.abstract":["The primary objective of this study is to elucidate the mechanism by which the reagent UCN-01 induces apoptosis when administered to leukemia cells along with HmG-CoA reductase inhibitors, mainly the statins. In this study, we demonstrated that exposure of leukemia cell lines to lovastatin (20 uM, 18 hours) and UCN-01 (100 nM, 18 hours) resulted in mitochondria dysfunction, procaspase 3 and 9 cleavage, and PAW degradation along with marked cytochrome C release and apoptosis. Although similar molecular mechanisms have not yet been confirmed in other cancers, our hypothesis holds that enhanced apoptotic effects of UCN-01 are due in part to lovastatin's ability to block formation of geranylgeranylpyrophosphate and farnesylpyrophosphate by interfering with the rate-limiting step of the mevalonate pathway. Geranylgeranylpyrophosphate and farnesylpyrophosphate induce post-translational modifications in RAS that anchor the protein to the cell membrane so that it acts as a signal transducer to the nucleus, promoting cell proliferation."],"dc:identifier":["https://doi.org/10.25772/MZXX-F811","https://scholarscompass.vcu.edu/etd/953"],"dc:rights":["© The Author"],"dc:subject":["farnesylpyrophosphate","UCN-01","geranylgeranylpyrophosphate","mitochondria dysfunction","apoptosis","Biomedical Engineering and Bioengineering","Engineering"],"dc:title":["HMG-CoA Reductase Inhibitors Act Synergistically with UCN-01 Through RAS Inhibition"],"thesis:degree_discipline":["Biomedical Engineering"],"thesis:degree_level":["Thesis"],"thesis:degree_name":["Master of Science"]},"updated_at":"2026-07-24T05:54:40Z"}