MATERIALS AND METHODS: Anti-cancer activity of a tocotrienol-rich fraction (TRF) and a tocotrienol-enriched fraction (TEF) isolated from palm oil, as well as pure vitamin E analogues (α-tocopherol, α-, δ- and γ-tocotrienols) were studied using highly aggressive triple negative MDA-MB-231 cells and oestrogen-dependent MCF-7 cells, both of human breast cancer cell lines. Cell population growth was evaluated using a Coulter particle counter. Cell death mechanism, poly(ADP-ribose) polymerase cleavage and levels of NF-κB were determined using commercial ELISA kits.
RESULTS: Tocotrienols exerted potent anti-proliferative effects on both types of cell by inducing apoptosis, the underlying mechanism of cell death being ascertained using respective IC50 concentrations of all test compounds. There was marked induction of apoptosis in both cell lines by tocotrienols compared to treatment with Paclitaxel, which was used as positive control. This activity was found to be associated with cleavage of poly(ADP-ribose) polymerase (a DNA repair protein), demonstrating involvement of the apoptotic cell death signalling pathway. Tocotrienols also inhibited expression of nuclear factor kappa-B (NF-κB), which in turn can increase sensitivity of cancer cells to apoptosis.
CONCLUSION: Tocotrienols induced anti-proliferative and apoptotic effects in association with DNA fragmentation, poly(ADP-ribose) polymerase cleavage and NF-κB inhibition in the two human breast cancer cell lines.
Methodology: Thirty rats were treated to receive 0.5 mL phosphate-buffered saline (group A, control), 0.5 mL corn oil (group B), 0.2% CPZ (group C), for 6 weeks, 0.2% CPZ for 3 weeks and then 200 mg/kg of Kv for 3 weeks (group D), or 200 mg/kg of Kv for 3 weeks followed by 0.2% CPZ for 3 weeks (group E). Rats were assessed for exploratory functions and anxiety-like behaviour before being euthanised and perfused transcardially with 4% paraformaldehyde. Prefrontal and hippocampal thin sections were stained in hematoxylin and eosin and cresyl fast violet stains.
Results: CPZ-induced demyelination resulted in behavioural impairment as seen by reduced exploratory activities, rearing behaviour, stretch attend posture, center square entry, and anxiogenic characteristics. Degenerative changes including pyknosis, karyorrhexis, neuronal hypertrophy, and reduced Nissl integrity were also seen. Animals treated with Kv showed significant improvement in behavioural outcomes and a comparatively normal cytoarchitectural profile.
Conclusion: Kv provides protective roles against CPZ-induced neurotoxicity through prevention of ribosomal protein degradation.
OBJECTIVE: Complexation of rHuKGF with mucoadhesive low molecular weight chitosan to protect rHuKGF from proteolysis and investigate the effect of chitosan-rHuKGF complex on the proliferation rate of FHs 74 Int cells.
METHODS: The interaction between chitosan and rHuKGF was studied by molecular docking. Malvern ZetaSizer Nano Zs and Fourier-Transform Infrared spectroscopy (FTIR) tests were carried out to characterize the chitosan-rHuKGF complex. In addition, SDS-PAGE was performed to investigate the interaction between chitosan-rHuKGF complex and pepsin. The effect of chitosan-rHuKGF complex on the proliferation rate of FHs 74 Int cells was studied by MTT assay.
RESULTS: Chitosan-rHuKGF complex was formed through the hydrogen bonding proven by the docking studies. A stable chitosan-rHuKGF complex was formed at pH 4.5 and was protected from proteolysis and assessed by SDS PAGE. According to the MTT assay results, chitosan-rHuKGF complex increased the cell proliferation rate of FHs 74 Int cells.
CONCLUSION: The developed complex improved the stability and the biological function of rHuKGF.