Sulforaphane (SFN) is an isothiocyanate (ITC) derived from glucosinolate (glucoraphanin) under the action of myrosinase when the plant tissue is damaged or chewed. Glucoraphanin is found in cruciferous vegetables such as broccoli, cauliflower, and cabbages. Epidemiological studies show that people who consume more cruciferous vegetables associate with a reduced risk of many types of cancer.
The chemopreventive effect has been attributed to the bioactivity of SFN. SFN is known to induce cell cycle arrest, apoptosis, autophagy and a number of antioxidant enzymes via the KEAP1-Nrf2-ARE pathway. However, SFN possesses hormetic effects on angiogenesis (low doses of SFN promote tube formation and high doses inhibit) (1,2). We have recently synthesised a novel silica (Si) quantum-dot (QD) conjugated-AITC, which abolished the low doses stimulatory effects (3). In this proposal, a range of selected ITCs such as AITC, BITC, Erucin, Iberin and PEITC will be investigated using a 3D co-culture of HUVECs and pericytes, and implantation of tumor (Bladder cancer and/or Liver cancer) cells onto the extraembryonic membranes of developing chick eggs - the chorioallantoic membrane (CAM) assay (4). One or two the most active ITCs will be further encapsulated using nano-techniques (5).
Hypothesis: Some forms of ITC may have stronger bioactivity than that of SFN and nano-encapsulated ITCs may possess enhanced anti- angiogenetic, and anti-tumor activities.
There are 3 main objectives:
(i) to determine the effectiveness of selected ITCs on cell proliferation, apoptosis and autophagy.
(ii) to compare the bioactivity of nano encapsulated ITCs with non-encapsulated form on angiogenesis (tube formation) using 3D co-culture HUVECs and pericytes model.
(iii) to assess the effectiveness of the most effective ITCs (and in nano forms) on angiogensis and tumor growth using the in vivo CAM assay.
For more information on the project supervisor, please go here: https://people.uea.ac.uk/en/persons/y-bao
Type of programme: PhD
Project start date: April 2019
Mode of study: Full time
Location: UEA, Bob Champion Research & Education Building
Entry requirements: Acceptable first-degree subject areas including Biochemistry, Cell/Molecular Biology, Cancer Biology/Oncology, and Nutrition. The standard minimum entry requirement is 2:1.
(1) Bao Y, Wang W, Zhou Z, Sun C. Benefits and risks of the hormetic effects of dietary isothiocyanates on cancer prevention. PLoS One. 2014; 9(12):e114764.
(2) Liu P, Atkinson SJ, Akbareian SE, Zhou Z, Munsterberg A, Robinson SD, Bao Y. Sulforaphane exerts anti-angiogenesis effects against hepatocellular carcinoma through inhibition of STAT3/HIF-1α/VEGF signalling. Sci Rep. 2017; 7(1):12651.
(3) Liu P, Behray M, Wang Q, Wang W, Zhou Z, Chao Y, Bao Y. Anti-cancer activities of allyl isothiocyanate and its conjugated silicon quantum dots. Sci Rep. 2018;8(1):1084.
(4) Storgard C, Mikolon D, Stupack DG. Angiogenesis assays in the chick CAM. Methods Mol Biol. 2005; 294:123-36.