{"id":{"repo_id":"twu","oai_identifier":"oai:twu-ir.tdl.org:11274/10679"},"canonical_url":"https://search.dev.ndltd.org/etd/twu/oai:twu-ir.tdl.org:11274/10679","repository":{"repo_id":"twu","name":"Texas Woman's University","base_url":"https://twu-ir.tdl.org/server/oai/request"},"display":{"title":"Impact of delta-tocotrienol on human melanoma cell proliferation","abstract":"The rate-limiting enzyme of the mevalonate pathway, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, provides essential intermediates for the prenylation or dolichylation of growth-related proteins including nuclear Ras, nuclear lamins, and growth factor receptors. d-δ-tocotrienol, a post-transcriptional down-regulator of HMG CoA reductase, suppresses the proliferation of marine B16 melanoma cells and human blood, breast, cervix, colon, liver, lung, lymph gland, nerve, pancreas, and prostate tumor cells. Dietary d-δ-tocotrienol suppresses the growth of implanted B16 melanomas without toxicity to host mice. We evaluated the impact of d-δ-tocotrienol on the proliferation of human A2058 and A375 melanoma cells. d-δ-tocotrienol induced dose-dependent suppression of the cell proliferation following 72 h incubation in 96-well plates with 50% inhibitory concentrations (IC50) of 37.5 ± 1.4 (A2058) and 22.3 ± 1.8 (A375) μmol/L, respectively. d-δ-tocotrienol-mediated cell cycle arrest at the G1 phase was accompanied by decreased expression of cyclin-dependent kinase 4. Concomitantly, procaspase-3 cleavage and morphological changes detected by fluorescence microscopy following acridine orange and ethidium bromide dual staining showed d-δ-tocotrienol-induced apoptosis in melanoma cells. Consequent to mevalonate deprivation and the putatively reduced prenylation and biological half-life of Ras protein, d-δ-tocotrienol induced concentration- and time dependent decrease in the expression of Ras. The impact of d-8-tocotrienol on A2058 cell proliferation was potentiated by lovastatin (IC50 = 3.1± 0.5 μmol/L), a competitive inhibitor of HMG CoA reductase. d-δ-tocotrienol may have potential application in melanoma chemoprevention and/or therapy.","abstract_html":"The rate-limiting enzyme of the mevalonate pathway, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, provides essential intermediates for the prenylation or dolichylation of growth-related proteins including nuclear Ras, nuclear lamins, and growth factor receptors. d-δ-tocotrienol, a post-transcriptional down-regulator of HMG CoA reductase, suppresses the proliferation of marine B16 melanoma cells and human blood, breast, cervix, colon, liver, lung, lymph gland, nerve, pancreas, and prostate tumor cells. Dietary d-δ-tocotrienol suppresses the growth of implanted B16 melanomas without toxicity to host mice. We evaluated the impact of d-δ-tocotrienol on the proliferation of human A2058 and A375 melanoma cells. d-δ-tocotrienol induced dose-dependent suppression of the cell proliferation following 72 h incubation in 96-well plates with 50% inhibitory concentrations (IC50) of 37.5 ± 1.4 (A2058) and 22.3 ± 1.8 (A375) μmol/L, respectively. d-δ-tocotrienol-mediated cell cycle arrest at the G1 phase was accompanied by decreased expression of cyclin-dependent kinase 4. Concomitantly, procaspase-3 cleavage and morphological changes detected by fluorescence microscopy following acridine orange and ethidium bromide dual staining showed d-δ-tocotrienol-induced apoptosis in melanoma cells. Consequent to mevalonate deprivation and the putatively reduced prenylation and biological half-life of Ras protein, d-δ-tocotrienol induced concentration- and time dependent decrease in the expression of Ras. The impact of d-8-tocotrienol on A2058 cell proliferation was potentiated by lovastatin (IC50 = 3.1± 0.5 μmol/L), a competitive inhibitor of HMG CoA reductase. d-δ-tocotrienol may have potential application in melanoma chemoprevention and/or therapy.","abstract_has_math":false,"creators":["Fernandes, Nicolle Valerie"],"institution":"Texas Woman's University","degree_name":"Doctor of Philosophy","degree_level":"Doctoral","degree_discipline":"Nutrition","degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":["Mo, Huanbiao"],"committee_members":["DiMarco, Nancy M.","Hynds, DiAnna L.","Grossie, Bruce","Vijayagopal, Parakat"],"year":2010,"date_issued":"2010-05","date_published":"2010-05","updated_at":"2026-07-24T05:05:17Z","subjects":["Health and environmental sciences","Biological sciences","Isoprenoids","Melanoma","d-delta-tocotrienol","Molecular biology","Nutrition"],"languages":["en_US"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/11274/10679","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.committeechair","label":"Committee Chair","values":["Mo, Huanbiao"]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["DiMarco, Nancy M.","Hynds, DiAnna L.","Grossie, Bruce","Vijayagopal, Parakat"]},{"key":"dc:creator","label":"Author","values":["Fernandes, Nicolle Valerie"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2018-11-08T17:05:33Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2018-11-08T17:05:33Z"]},{"key":"dc:date.issued","label":"Date","values":["2010-05"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Nutrition"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Texas Woman's University"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Health and environmental sciences","Biological sciences","Isoprenoids","Melanoma","d-delta-tocotrienol","Molecular biology","Nutrition"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en_US"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/11274/10679"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The rate-limiting enzyme of the mevalonate pathway, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, provides essential intermediates for the prenylation or dolichylation of growth-related proteins including nuclear Ras, nuclear lamins, and growth factor receptors. d-δ-tocotrienol, a post-transcriptional down-regulator of HMG CoA reductase, suppresses the proliferation of marine B16 melanoma cells and human blood, breast, cervix, colon, liver, lung, lymph gland, nerve, pancreas, and prostate tumor cells. Dietary d-δ-tocotrienol suppresses the growth of implanted B16 melanomas without toxicity to host mice. We evaluated the impact of d-δ-tocotrienol on the proliferation of human A2058 and A375 melanoma cells. d-δ-tocotrienol induced dose-dependent suppression of the cell proliferation following 72 h incubation in 96-well plates with 50% inhibitory concentrations (IC50) of 37.5 ± 1.4 (A2058) and 22.3 ± 1.8 (A375) μmol/L, respectively. d-δ-tocotrienol-mediated cell cycle arrest at the G1 phase was accompanied by decreased expression of cyclin-dependent kinase 4. Concomitantly, procaspase-3 cleavage and morphological changes detected by fluorescence microscopy following acridine orange and ethidium bromide dual staining showed d-δ-tocotrienol-induced apoptosis in melanoma cells. Consequent to mevalonate deprivation and the putatively reduced prenylation and biological half-life of Ras protein, d-δ-tocotrienol induced concentration- and time dependent decrease in the expression of Ras. The impact of d-8-tocotrienol on A2058 cell proliferation was potentiated by lovastatin (IC50 = 3.1± 0.5 μmol/L), a competitive inhibitor of HMG CoA reductase. d-δ-tocotrienol may have potential application in melanoma chemoprevention and/or therapy."]},{"key":"dc:title","label":"Title","values":["Impact of delta-tocotrienol on human melanoma cell proliferation"]}]}],"canonical_facts":{"dc:contributor.committeechair":["Mo, Huanbiao"],"dc:contributor.committeemember":["DiMarco, Nancy M.","Hynds, DiAnna L.","Grossie, Bruce","Vijayagopal, Parakat"],"dc:creator":["Fernandes, Nicolle Valerie"],"dc:date.accessioned":["2018-11-08T17:05:33Z"],"dc:date.available":["2018-11-08T17:05:33Z"],"dc:date.issued":["2010-05"],"dc:description.abstract":["The rate-limiting enzyme of the mevalonate pathway, 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, provides essential intermediates for the prenylation or dolichylation of growth-related proteins including nuclear Ras, nuclear lamins, and growth factor receptors. d-δ-tocotrienol, a post-transcriptional down-regulator of HMG CoA reductase, suppresses the proliferation of marine B16 melanoma cells and human blood, breast, cervix, colon, liver, lung, lymph gland, nerve, pancreas, and prostate tumor cells. Dietary d-δ-tocotrienol suppresses the growth of implanted B16 melanomas without toxicity to host mice. We evaluated the impact of d-δ-tocotrienol on the proliferation of human A2058 and A375 melanoma cells. d-δ-tocotrienol induced dose-dependent suppression of the cell proliferation following 72 h incubation in 96-well plates with 50% inhibitory concentrations (IC50) of 37.5 ± 1.4 (A2058) and 22.3 ± 1.8 (A375) μmol/L, respectively. d-δ-tocotrienol-mediated cell cycle arrest at the G1 phase was accompanied by decreased expression of cyclin-dependent kinase 4. Concomitantly, procaspase-3 cleavage and morphological changes detected by fluorescence microscopy following acridine orange and ethidium bromide dual staining showed d-δ-tocotrienol-induced apoptosis in melanoma cells. Consequent to mevalonate deprivation and the putatively reduced prenylation and biological half-life of Ras protein, d-δ-tocotrienol induced concentration- and time dependent decrease in the expression of Ras. The impact of d-8-tocotrienol on A2058 cell proliferation was potentiated by lovastatin (IC50 = 3.1± 0.5 μmol/L), a competitive inhibitor of HMG CoA reductase. d-δ-tocotrienol may have potential application in melanoma chemoprevention and/or therapy."],"dc:identifier.uri":["https://hdl.handle.net/11274/10679"],"dc:language.iso":["en_US"],"dc:subject":["Health and environmental sciences","Biological sciences","Isoprenoids","Melanoma","d-delta-tocotrienol","Molecular biology","Nutrition"],"dc:title":["Impact of delta-tocotrienol on human melanoma cell proliferation"],"dc:type":["Dissertation"],"thesis:degree_discipline":["Nutrition"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["Doctor of Philosophy"],"thesis:institution_name":["Texas Woman's University"]},"updated_at":"2026-07-24T05:05:17Z"}