The food that we consume contain many dietary compounds which are biologically active. In this thesis we will discuss the biological effects of dietary compounds and the mechanisms behind their activities.
First, we studied on the anti-metastatic effects of curcumin, a dietary compound derived from turmeric, through lymphangiogenesis inhibition. Curcumin inhibited vascular endothelial growth factor-C (VEGF-C)-induced lymphangiogenesis in vivo and in vitro. Curcumin inhibited lymphangiogenesis, in part through suppression of proliferation, cell cycle progression and migration of lymphatic endothelial cells. Curcumin inhibited expressions of VEGF receptors (VEGFR2 and VEGFR3), as well as down-stream signaling such as phosphorylation of ERK and FAK. Finally, curcumin sulfate and curcumin glucuronide, two major metabolites of curcumin in vivo, had little inhibitory effect on proliferation of HMVEC-dLy cells. Our results demonstrate that curcumin inhibits lymphangiogenesis in vitro and in vivo, which could contribute to the anti-metastatic effects of curcumin.
Next, we investigated the mechanisms underlying the cytotoxic activity of tert-butylhydroquinone (TBHQ), a widely used synthetic food antioxidant. Here we found that the biological effects of TBHQ are mainly mediated by its oxidative conversion to a quinone metabolite tert-butylquinone (TBQ). Co-addition of cupric ion (Cu2+) enhanced, whereas ethylenediaminetetraacetic acid (EDTA) suppressed the oxidative conversion of TBHQ to TBQ, and the biological activities of TBHQ in MC38 colon cancer cells. Finally, a structure and activity relationship study was done and together, these results suggest that the biological activities of TBHQ and other para-hydroquinones are mainly mediated by their oxidative metabolism to generate more biologically active quinone metabolites.
| Identifer | oai:union.ndltd.org:UMASS/oai:scholarworks.umass.edu:masters_theses_2-1657 |
| Date | 09 July 2018 |
| Creators | Sukamtoh, Elvira |
| Publisher | ScholarWorks@UMass Amherst |
| Source Sets | University of Massachusetts, Amherst |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Masters Theses |
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