ANTICANCER POTENTIALS OF ISOTHIOCYANATES, DITERPENOIDS, AND THEIR MOLECULAR MECHANISMS OF INTERACTIONS

High consumption of cruciferous vegetables can reduce the risk of cancer. This protection is attributed to high level of glucocinolates 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 previously shown that the dietary isothiocyanate sulforaphane (SFN) has such biphasic effects on cell proliferation, migration, invasion and angiogenesis (Bao et al., PloS One 2014; Liu et al., Sci Rep. 2017; Wang et al., Food & Function 2022), whereas ITCs in nanoparticle form do not have this hormetic property. Co-encapsulation of cisplatin and SFN also produced a greater anti-cancer effect (Xu et al., ACS Nano 2019).  

Recently, we have shown that Scutebarbatine A (a diterpenoid) from Scutellaria barbata exhibited selectivity towards tumour cells with reduced or no toxicity towards corresponding normal cells (Tomlinson et al., 2022). Scutellaria barbata extracts can induce apoptosis and have the potential to chemosensitize cancer cells to other anti-cancer treatments and overcome multi-drug resistance.

In this PhD project, we will investigate: (1) the mechanisms of ITCs and diterpenoids using in vitro cell culture models (e.g. breast cancer and normal cell lines), key signalling pathways such as Nrf2/Keap1-ARE, NF-κB and Sirtuin-FOXO; (2) synergistic interactions between ITCs and diterpenoids (or other more active components from medicinal plants), and to define if phytochemicals are better to act as adjuvant anti-cancer drugs; and (3) molecular mechanisms of interactions between ITCs and herbal medicine in cancer therapy.

Novel targets will be unveiled using RNA-Seq, Omics technology and conventional approaches established at UEA and Norwich Research Park. The results of this study will help to define beneficial levels of isothiocyanates and medicinal plants in cancer prevention and treatment.  Moreover, an improved understanding of the hormetic properties of bioactive plant phytochemicals may help to understand their health-promoting potential in the management of cancer.