Non-small cell lung cancer (NSCLC) is most hostile and leading cause of cancer deaths in the United States. Clinical data has demonstrated that 30 % of NSCLC patients have increased Notch activity and 10% of NSCLC have gain-of-function mutation on Notch-1 gene. Our data demonstrated that delta-tocotrienol could inhibit NSCLC cells proliferation, invasion and induce apoptosis by down-regulation of the Notch-1 signaling pathway. Using microRNA microarray and microRNA transfection, our findings further suggest that delta-tocotrienol is a non-toxic activator of miR-34a which can inhibit NSCLC cell proliferation, induce apoptosis, and inhibit invasion. Last but not the least, We observed that delta-tocotrienol individually or in combination with cisplatin exhibited potent anticancer abilities in NSCLC cells by down-regulating oncogenic pathways such as Notch-1 and NF-ĸB pathways and up-regulating the tumor suppressor pathways such as Bcl-2, caspase-3. Decreased NF- κB activity was observed in both cell lines in combination treatment along with significantly reduced levels of angiogenic factors MMP-9, VEGF thus offering a potential starting point for the design of novel anticancer agents. Overall, our results suggest that delta-tocotrienol could be a promising approach for designing tailored novel combination therapies for the treatment of human NSCLC.
","abstract_html":"<p>Non-small cell lung cancer (NSCLC) is most hostile and leading cause of cancer deaths in the United States. Clinical data has demonstrated that 30 % of NSCLC patients have increased Notch activity and 10% of NSCLC have gain-of-function mutation on Notch-1 gene. Our data demonstrated that delta-tocotrienol could inhibit NSCLC cells proliferation, invasion and induce apoptosis by down-regulation of the Notch-1 signaling pathway. Using microRNA microarray and microRNA transfection, our findings further suggest that delta-tocotrienol is a non-toxic activator of miR-34a which can inhibit NSCLC cell proliferation, induce apoptosis, and inhibit invasion. Last but not the least, We observed that delta-tocotrienol individually or in combination with cisplatin exhibited potent anticancer abilities in NSCLC cells by down-regulating oncogenic pathways such as Notch-1 and NF-ĸB pathways and up-regulating the tumor suppressor pathways such as Bcl-2, caspase-3. Decreased NF- κB activity was observed in both cell lines in combination treatment along with significantly reduced levels of angiogenic factors MMP-9, VEGF thus offering a potential starting point for the design of novel anticancer agents. Overall, our results suggest that delta-tocotrienol could be a promising approach for designing tailored novel combination therapies for the treatment of human NSCLC.</p>","abstract_has_math":false,"creators":["Ji, Xiangming"],"institution":null,"degree_name":"Ph.D.","degree_level":"Open Access Dissertation","degree_discipline":"Nutrition and Food Science","degree_department":null,"school":null,"contributors":["Smiti Gupta"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2012,"date_issued":"2012-01-01T08:00:00Z","date_published":"2012-01-01T08:00:00Z","updated_at":"2026-07-24T05:59:11Z","subjects":["delta-tocotrienol, lung cancer, Notch-1","Nutrition"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.wayne.edu/oa_dissertations/546","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Smiti Gupta"]},{"key":"dc:creator","label":"Author","values":["Ji, Xiangming"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2012-01-01T08:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Nutrition and Food Science"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Open Access Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["delta-tocotrienol, lung cancer, Notch-1","Nutrition"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.wayne.edu/oa_dissertations/546"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Non-small cell lung cancer (NSCLC) is most hostile and leading cause of cancer deaths in the United States. Clinical data has demonstrated that 30 % of NSCLC patients have increased Notch activity and 10% of NSCLC have gain-of-function mutation on Notch-1 gene. Our data demonstrated that delta-tocotrienol could inhibit NSCLC cells proliferation, invasion and induce apoptosis by down-regulation of the Notch-1 signaling pathway. Using microRNA microarray and microRNA transfection, our findings further suggest that delta-tocotrienol is a non-toxic activator of miR-34a which can inhibit NSCLC cell proliferation, induce apoptosis, and inhibit invasion. Last but not the least, We observed that delta-tocotrienol individually or in combination with cisplatin exhibited potent anticancer abilities in NSCLC cells by down-regulating oncogenic pathways such as Notch-1 and NF-ĸB pathways and up-regulating the tumor suppressor pathways such as Bcl-2, caspase-3. Decreased NF- κB activity was observed in both cell lines in combination treatment along with significantly reduced levels of angiogenic factors MMP-9, VEGF thus offering a potential starting point for the design of novel anticancer agents. Overall, our results suggest that delta-tocotrienol could be a promising approach for designing tailored novel combination therapies for the treatment of human NSCLC.
"]},{"key":"dc:title","label":"Title","values":["Intervention of non-small cell line cancer oncogenic pathways with delta-tocotrienol"]}]}],"canonical_facts":{"dc:contributor":["Smiti Gupta"],"dc:creator":["Ji, Xiangming"],"dc:date.available":["2012-01-01T08:00:00Z"],"dc:description.abstract":["Non-small cell lung cancer (NSCLC) is most hostile and leading cause of cancer deaths in the United States. Clinical data has demonstrated that 30 % of NSCLC patients have increased Notch activity and 10% of NSCLC have gain-of-function mutation on Notch-1 gene. Our data demonstrated that delta-tocotrienol could inhibit NSCLC cells proliferation, invasion and induce apoptosis by down-regulation of the Notch-1 signaling pathway. Using microRNA microarray and microRNA transfection, our findings further suggest that delta-tocotrienol is a non-toxic activator of miR-34a which can inhibit NSCLC cell proliferation, induce apoptosis, and inhibit invasion. Last but not the least, We observed that delta-tocotrienol individually or in combination with cisplatin exhibited potent anticancer abilities in NSCLC cells by down-regulating oncogenic pathways such as Notch-1 and NF-ĸB pathways and up-regulating the tumor suppressor pathways such as Bcl-2, caspase-3. Decreased NF- κB activity was observed in both cell lines in combination treatment along with significantly reduced levels of angiogenic factors MMP-9, VEGF thus offering a potential starting point for the design of novel anticancer agents. Overall, our results suggest that delta-tocotrienol could be a promising approach for designing tailored novel combination therapies for the treatment of human NSCLC.
"],"dc:identifier":["https://digitalcommons.wayne.edu/oa_dissertations/546"],"dc:subject":["delta-tocotrienol, lung cancer, Notch-1","Nutrition"],"dc:title":["Intervention of non-small cell line cancer oncogenic pathways with delta-tocotrienol"],"thesis:degree_discipline":["Nutrition and Food Science"],"thesis:degree_level":["Open Access Dissertation"],"thesis:degree_name":["Ph.D."]},"updated_at":"2026-07-24T05:59:11Z"}