Engineering of polyphenol metabolism in tomatoes to enhance anti-cancer activities

Anthocyanins are polyphenolic plant pigments that are responsible for much of the attractive colour displays found in many flowers, fruit and vegetables. Anthocyanins are divided into different classes based on the number of hydroxyl groups on their phenyl B-ring and subsequent side chain modifications. It has been shown in our laboratory that the introduction of the regulatory genes Delila and Rosea1 activates the biosynthetic pathway leading to accumulation of trihydroxylated anthocyanins in tomatoes. Tomato DFR substrate specificity for trihydroxylated precursors prevents the formation of other anthocyanin classes. By inhibiting the activity of F3’5’H, blocking biosynthesis of trihydroxylated anthocyanins, and introducing a non-specific DFR from A. majus, I developed two transgenic tomato lines that produced mono- and dihydroxylated anthocyanins. My work demonstrated that tomatoes could be enriched with different classes of anthocyanins using a metabolic engineering approach. Dietary consumption of plant secondary metabolites such as anthocyanins and other polyphenols are linked to a reduced risk of developing chronic, non-communicable diseases such as cancer, type 2 diabetes and cardiovascular diseases. High-anthocyanin tomato extracts induced cell death, cell cycle alteration and apoptosis in the human breast cancer cell lines, MCF-7 and MDA-MB-231, whilst WT tomato extracts exerted no biological effects. Purified anthocyanins and polyphenolic compounds had no or little effect on the metabolic status of breast cancer cells, suggesting that anthocyanins exert their biological effects in synergy with other components in the food matrix. Polyphenolic compounds may act as chemosensitizers for the treatment of tumours with chemotherapeutic agents. Co-treatment of breast cancer cells with the chemotherapeutic agents, doxorubicin or roscovitine, and high-anthocyanin or -resveratrol tomato extracts showed that dietary polyphenols might potentiate the effects of pharmacological agents in vitro. This work demonstrated that the health benefits of dietary plants can be significantly improved through nutritional enrichment with plant bioactives using metabolic engineering.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

University of East Anglia

Year dc:date.issued

2013

Author dc:creator

• Bulling, Katharina

Language dc:language

en