Anticancer activity of sulforaphane and allyl isothiocyanate- conjugated silicon quantum dots

Liu, Peng (2017) Anticancer activity of sulforaphane and allyl isothiocyanate- conjugated silicon quantum dots. Doctoral thesis, University of East Anglia.

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Abstract

Dietary isothiocyanates (ITCs) from cruciferous vegetables (CVs) have been shown to possess chemopreventive and chemotherapeutic effects in many cellular and animal studies but with only limited success in humans. The aim of this thesis is to further evaluate the bioactivities of ITCs and the mechanisms behind, and the potential of multi-functional nano-conjugates to maximize the beneficial effects of ITCs in cancer therapy.
The effects of sulforaphane (SFN), one of the most studied ITCs, were examined on human hepatocytes (HHL5) and hepatocarcinoma (HepG2) cells. Results showed that SFN was more toxic towards HHL5 than HepG2, and that the high basal levels of Nrf2/GSH/ROS enabled HepG2 cells to benefit from the protective effects of SFN against H2O2-induced cell death, apoptosis and DNA damage. Three of the metabolites of SFN were also examined in terms of their anticancer activities, and were demonstrated to exhibit similar cytoprotective activity, but weaker cytotoxic effects than SFN. Allyl isothiocyanate (AITC), another common dietary ITC, showed biphasic effects on cell viability, DNA damage and migration in HepG2 cells, and on endothelial cell tube formation in a 3D model. siRNA knockdown of Nrf2 and GSH inhibition abolished the stimulatory effects of low dose AITC on cell migration as well as low dose AITC induced protection against DNA damage. The lack of selectivity and the biphasic effects of ITCs could present undesirable risks in the context for cancer prevention and treatment.
The bioactivities of novel AITC-conjugated silicon quantum dots (AITC-SiQDs) were compared with AITC, and their cellular uptake was monitored by detecting the intrinsic fluorescence of SiQDs. AITC-SiQDs demonstrated similar activity as AITC at high doses whilst lacking the low dose stimulatory effects. In addition, AITC-SiQDs induced a long-lasting activation of Nrf2 via translocation into the nucleus, which correlated positively with their cellular uptake. ROS were involved in the anticancer effects of AITC-SiQDs. Taken together, these data provide novel insights into the anticancer properties of ITCs and highlight the possibility of application of nanotechnology to optimize their potential in cancer treatment.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User:	Bruce Beckett
Date Deposited:	20 Jul 2018 11:03
Last Modified:	20 Jul 2018 11:03
URI:	https://ueaeprints.uea.ac.uk/id/eprint/67691
DOI:

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