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.

Materials and 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).

Conclusion: Tocotrienol oxazine derivatives may provide benefit as therapeutic agents against breast cancer.

Keywords: AKT; NFκB; Tocotrienols; breast cancer; lipid nanoemulsion; oxazine derivatives; vitamin E.