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Document Type

Open Access Dissertation

Degree Name

Doctor of Philosophy (PhD)

Degree Program

Food Science

Year Degree Awarded

2017

Month Degree Awarded

May

First Advisor

Hang Xiao

Subject Categories

Biology | Food Science

Abstract

Isothiocyanates (ITCs) such as allyl isothiocyanate (AIT) and sulforaphane (SFN) are well-known bioactives with wide range of beneficial properties, which may be consumed simultaneously through diets containing cruciferous vegetables. However, biological activities of ITCs in combinations had not been well defined. The present study evaluated the potential efficacy of AIT, SFN and their combinations on three important biological properties: anticancer, anti-inflammation and antioxidant.

Our results showed that the combination between AIT and SFN led to a stronger growth inhibition on A549 non-small cell lung cancer cells than treatments with the individual compounds. The enhanced effect was proved to be synergistic by isobologram analysis. Flow cytometry analysis demonstrated that the combination treatment caused more extensive cell cycle arrest and cellular apoptosis in the cancer cells than the singular treatment. In addition, a synergy between AIT and SFN was also observed in their anti-cell migration. It is noteworthy that the AIT-SFN combination resulted in the production of intracellular reactive oxygen species (ROS), which might contribute to their inhibitory effects on cancer cells.

In terms of anti-inflammation, the combination of AIT and SFN both pairing between themselves (AIT-SFN), and pairing with other dietary bioactives (AIT-CUR, AIT-LUT, and SFN-LUT) enhanced this beneficial property in comparison to a single compound utilization in lipopolysaccharide-induced RAW 264.7 macrophages. We observed dose-dependent and synergistic inhibition of pro-inflammatory molecules production such as nitric oxide, and interleukin-6. Western blotting showed corresponding information that the combined treatment reduced the expression levels of pro-inflammatory proteins and increased the expression of an antioxidative protein, which could contribute to their anti-inflammatory properties as well.

In addition, pretreatment of RAW 264.7 cells with the AIT-SFN combination provided synergistic cytoprotective effects against tert-butyl hydroperoxide-induced oxidative damage by increasing antioxidant effects, decreasing cellular ROS, and increasing viability of RAW 264.7 cells. These protective properties were completed through phase 2 antioxidant and detoxification proteins, some of which had more dominant effects than the others, under a partial regulation of Nrf2, and NF-κB transcription factors.

Overall, this study proved a potential enhancement of dietary ITCs in combinations on biological activities and provided information for developing functional foods for health benefits.

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