title: Oxazine derivatives of γ- and δ-tocotrienol display enhanced anticancer activity in vivo.
abstract: BACKGROUND
  Oxazine derivatives of tocotrienols display enhanced anticancer activity. Studies were conducted to further characterize these effects in vivo.
  
  
  METHODS
  Tetrazolium assay was used to determine the inhibitory effects of oxazine derivatives of γ-tocotrienol and δ-tocotrienol in vitro. These compounds were further formulated as lipid nanoemulsions and intralesional administration was used to examine their anticancer activity in vivo.
  
  
  RESULTS
  Tocotrienol oxazine derivatives significantly inhibited +SA mammary tumor growth in syngeneic mice as compared to their respective parent compound, and these effects were associated with a reduction in cell proliferation and survival (phosphorylated protein kinase B (AKT) and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), and cyclooxygenase-2 (COX2) and cell-cycle progression (cyclin D1, cyclin-dependent kinase 2 (CDK2), CDK4 and CDK6) markers, and increase in cell-cycle arrest proteins (p21 and p27).
  
  
  CONCLUSIONS
  Tocotrienol oxazine derivatives may provide benefit as therapeutic agents against breast cancer.
authors.affiliation: School of Pharmacy, University of Louisiana at Monroe, Monroe, LA, U.S.A.
authors.forename: Suryatheja
authors.initials: S
authors.lastname: Ananthula
authors.affiliation: School of Pharmacy, University of Louisiana at Monroe, Monroe, LA, U.S.A.
authors.forename: Parash
authors.initials: P
authors.lastname: Parajuli
authors.affiliation: School of Pharmacy, University of Louisiana at Monroe, Monroe, LA, U.S.A.
authors.forename: Fathy A
authors.initials: FA
authors.lastname: Behery
authors.affiliation: School of Pharmacy, University of Louisiana at Monroe, Monroe, LA, U.S.A.
authors.forename: Alaadin Y
authors.initials: AY
authors.lastname: Alayoubi
authors.affiliation: School of Pharmacy, University of Louisiana at Monroe, Monroe, LA, U.S.A.
authors.forename: Khalid A
authors.initials: KA
authors.lastname: El Sayed
authors.affiliation: School of Pharmacy, University of Louisiana at Monroe, Monroe, LA, U.S.A.
authors.forename: Sami
authors.initials: S
authors.lastname: Nazzal
authors.affiliation: School of Pharmacy, University of Louisiana at Monroe, Monroe, LA, U.S.A. sylvester@ulm.edu.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Sylvester
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D002839:Chromans / Q000737:chemistry / Q000627:therapeutic use*; D005260:Female; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010078:Oxazines / Q000737:chemistry / Q000627:therapeutic use*; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D002839:Chromans; D010078:Oxazines; D014810:Vitamin E; C082097:tocotrienol, delta; C013649:plastochromanol 8
keywords: AKT; NFκB; Tocotrienols; breast cancer; lipid nanoemulsion; oxazine derivatives; vitamin E