Interactions between dietary isothiocyanates and anti-cancer drug sorafenib in breast cancer (BAOY_U23MED204350) at University of East Anglia on FindAPhD.com

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Dr Y Bao, Prof D Pshezhetskiy No more applications being accepted Funded PhD Project (Students Worldwide)

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Norwich United Kingdom Biochemistry Cancer Biology Cell Biology

About the Project

High consumption of cruciferous vegetables can reduce the risk of cancer. The protection has been attributed to high level of glucosinolates and their breakdown products isothiocyanates (ITCs) in cruciferous vegetables. However, isothiocyanates have been shown to possess hormetic properties (low dose stimulation and high dose inhibition) of cell growth. We have shown that dietary isothiocyanates at higher dose possess anti-cancer effects on cell migration, invasion, and angiogenesis.

Breast cancer is one of the most common malignancies in women. Particularly, triple negative breast cancer is more challenging for treatment. Recently, combinational therapy has become a cornerstone in cancer treatment to potentiate therapeutic effectiveness and overcome drug resistance and metastasis. Sorafenib (SOR), a novel multi kinase inhibitor, is broadly used alone or in combination with other therapeutics to combat breast cancer. We have shown dietary ITCs such as sulforaphane (SFN) potentiate the efficacy of cisplatin (CDDP) against breast cancer.

In this PhD project, we will investigate:

(1) The effect of combined ITC and SOR treatments on breast cancer will be studied using MDA-MB-231, MCF-7, and a normal breast cell line MCF-10A cells. Cell viability assay, colony formation, and flow cytometry analysis will be used initially to evaluate the anti-cancer effects.

(2) Cell migration, invasion, and angiogenesis will be studied using arrange of assays established in-house. Free drugs will be compared with nano-encapsulated ITCs and the combined forms such as ITC+SOR.

(3) Molecular mechanisms of interactions between ITCs and anti-cancer drugs in cancer therapy. Antibody arrays, RT-PCR and Western blotting will be employed to study the underline mechanism.

(4) Finally, a mouse xenograft model will be employed to assess the efficacy of various combinations of ITCs and SOR including nano-encapsulated forms on cancer therapeutics.

Combining BITC and SOR treatment into a nanoparticle delivery system could enhance the treatment effectiveness against spheroid models and reduce toxicity to normal cells, and improved understanding of the mechanism of bioactive phytochemicals in prevention and treatment of cancer. This study will provide useful information for a further clinical trial using combined therapy.

For more information on the supervisor for this project, please visit the UEA website www.uea.ac.uk

Primary Supervisor: Prof Yongping Bao ([Email Address Removed])

Start date: October 2023

Funding Notes

This postgraduate research opportunity is funded by the Cancer Prevention Research Trust for three years. The studentship includes a stipend of £17,668 (2022/23 rate) and £1,000 per annum for research training. Only UK (Home) tuition fees are covered, other applicants will need to secure additional funding to fund the difference between UK and overseas tuition fees (details of tuition fees are available on our website: https://www.uea.ac.uk/study/fees-and-funding/fees).

References

i) Xu Y, Han X, Li Y, Min H, Zhao X, Zhang Y, Qi Y, Shi Y, Qi S, Bao Y, Nie G. Sulforaphane Mediates Glutathione Depletion via Polymeric Nanoparticles to Restore Cisplatin Chemosensitivity. ACS Nano, 2019;13(11):13445-13455. doi: 10.1021/acsnano.9b07032
ii) Wang Y et al., Biphasic effect of sulforaphane on angiogenesis in hypoxia via modulation of both Nrf2 and mitochondrial dynamics. Food & Function. 2022. 13, 2884-2898. https://doi.org/10.1039/D1FO04112F
iii) 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.
iv) 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. doi: 10.1038/s41598-018-19353-7.
v) Wang Q, Alshaker H, Böhler T, Srivats S, Chao Y, Cooper C, Pchejetski D. Core shell lipid-polymer hybrid nanoparticles with combined docetaxel and molecular targeted therapy for the treatment of metastatic prostate cancer. Sci Rep. 2017;7(1):5901. doi:10.1038/s41598-017-06142-x.