Source: KANSAS STATE UNIV submitted to NRP
PROTECTING AGAINST INFLAMMATION-INDUCED COLORECTAL CANCER RISK BY UNIQUE NUTRACEUTICAL ANTHOCYANIN-ENRICHED BIOENGINEERED TOMATOES
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
ACTIVE
Funding Source
Reporting Frequency
Annual
Accession No.
1032124
Grant No.
2024-67017-42463
Cumulative Award Amt.
$650,000.00
Proposal No.
2023-08266
Multistate No.
(N/A)
Project Start Date
Jun 1, 2024
Project End Date
May 31, 2029
Grant Year
2024
Program Code
[A1343]- Food and Human Health
Recipient Organization
KANSAS STATE UNIV
(N/A)
MANHATTAN,KS 66506
Performing Department
(N/A)
Non Technical Summary
The goal of this study is to delineate evidence and mechanisms by which the anthocyanin-enriched transgenic tomatoes may protect against colorectal cancer through anthocyanins in cell culture and animal models. Successful completion of this study will provide scientific evidence for the health benefits of anthocyanin-enriched bioengineered transgenic tomatoesfor anticancer activities. In addition, this study will encompass regular publications in reputable journals and train postdoctoral fellow and graduatestudents. Another important impact of this work is to promote agricultural farming and marketing opportunities for novel tomato varieties as functional food products for cancer prevention.
Animal Health Component
10%
Research Effort Categories
Basic
90%
Applied
10%
Developmental
0%
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
70114601010100%
Knowledge Area
701 - Nutrient Composition of Food;

Subject Of Investigation
1460 - Tomato;

Field Of Science
1010 - Nutrition and metabolism;
Goals / Objectives
The goal of this proposal is to explore chemopreventive efficacy of anthocyanin-enriched bioengineered tomatoes as a novel nutraceutical food for the prevention of colorectal cancer by targeting at the inflammatory cytokine-stimulated proliferation and anti-apoptosis signaling.
Project Methods
Three aims will be approached. In Aim 1,we will grow the anthocyanin-enriched bioengineered tomatoesand extract anthocyanins from the novel anthocyanin-enriched bioengineered tomatoesto assess the impact of bioengineered tomatoanthocyanins on cellular uptake and metabolism by LC-MS/MS and TNFα-induced signaling with selective knockdown by siRNA and pharmacological inhibitors in both normal colonic epithelial FHC cells and colonic adenocarcinoma SW480 cells. We will further co-culture colonic epithelial cells with macrophage THP1 cells for the impact of bioengineered tomatoanthocyanins on local macrophage-released cytokine inflammation and signaling in an advanced 3D organoid model. In Aim 2,we will measure bioavailability of dietary bioengineered tomatoanthocyanins in the blood, bioaccessibility of dietary bioengineered tomato anthocyanins to the colon tissues, effects of dietary anthocyanin-enriched bioengineered tomatoeson systemic metabolome, and effect of dietary anthocyanin-enriched bioengineered tomatoeson LPS-induced cytokine signaling in the colon tissues. In Aim 3,we will determine the dose-response and contribution of gut microbiota by antibiotic depletion, evaluate the effect of dietary anthocyanin-enriched bioengineered tomatoes on microbial composition by metagenomic sequencing, and ascertain anti-neoplastic mechanisms on colon tumorigenesis.

Progress 06/01/24 to 05/31/25

Outputs
Target Audience:The unique anthocyanin-enriched bioengineered tomato varieties developed for farmers, the new value-added healthy products for consumers, and the advanced 3D cell culture and animal model for scientific community. This proposal will not only develop the unique anthocyanin-enriched bioengineered tomatoes but also evaluate their impact on colonic cancer prevention and underlying mechanisms in both in vitro and in vivo models. Furthermore, graduate students and postdoctoral fellows will be trained through this project. The results will be presented in national or international conferences and published in peer-reviewed scientific journals. Changes/Problems:One of the co-Project Directors, Dr. Xiuzhi Susan Sun, has retired from Kansas State University. As a result, her role as co-Project Director for this project has been transferred to Dr. Donghai Wang. This change, outlined in the letter dated February 27, 2025, has been reviewed and approved by the office and the NIFA cognizant program official, Mark Heap, on March 4, 2025. What opportunities for training and professional development has the project provided?Several graduate and undergraduate students, along with one research associate, participated in this project and received training in various areas, including novel transgenic tomato line development, anthocyanin extraction and analysis, cell culture treatments, and manuscript development and publication. How have the results been disseminated to communities of interest?The results of this research are primarily disseminated through peer-reviewed journal publications and national or international conference presentations. To date, one peer-reviewed article has been published in Foods. What do you plan to do during the next reporting period to accomplish the goals?The studies planned for the upcoming year will focus on addressing the remaining aspects of Objective 1. Specifically, we will continue investigating the anti-cancer mechanisms of anthocyanin-enriched transgenic tomato extracts in both normal colonic epithelial cells and colonic adenocarcinoma cells using both traditional 2D and advanced 3D cell culture systems. Our primary approach will be to examine the suppression of inflammatory cytokine-induced mitogenic signaling in vitro. All proposed studies will proceed as outlined in the original research plan.

Impacts
What was accomplished under these goals? Supported by this five-year USDA NIFA research project, several tasks from Objective 1 are being investigated in parallel for this first-year report. We have developed novel transgenic tomato lines and analyzed their anthocyanin profiles and content using HPLC. These lines are now ready for use in cell culture studies and upcoming animal feed experiments. To initiate our research, we conducted a comprehensive review of recent literature and published a review paper summarizing our progress and outlining our research plan for the next one to five years. Concurrently, we have continued exploring the anti-inflammatory effects of anthocyanin-enriched transgenic tomato extracts and their potential metabolites in both normal colonic epithelial FHC cells and adenocarcinoma SW480 cells. The potential mechanisms by which these extracts and/or their metabolites contribute to cancer cell inhibition will be further assessed in next year's 3D cell culture studies. All research activities have been conducted in full alignment with the original proposal, without modification.

Publications

  • Type: Peer Reviewed Journal Articles Status: Published Year Published: 2024 Citation: Md Suzauddula, Kaori Kobayashi, Sunghun Park, Xiuzhi Susan Sun, Weiqun Wang. Bioengineered Anthocyanin-enriched tomatoes: a novel approach to colorectal cancer prevention. Foods 2024; 13(18), 2991. https://doi.org/10.3390/foods13182991