Inhibitory Effects of Differentially Cultivated Carrots on AOM/DSS-Induced Colorectal Cancer Via Modulation of Inflammation, Apoptosis, and Gut Microbiota | Chapter 1 | Molecular Mechanisms and Signaling Pathways of the Anti-inflammatory Effects of Functional Foods

 

Background: Carrot (Daucus carota) is a widely consumed vegetable rich in dietary fibre, vitamins, minerals, and antioxidant compounds. Carrots contain fibre and bioactive phytochemicals that have been associated with anti-inflammatory and anti-proliferative activities in preclinical settings. Beta-carotene, a prominent carotenoid in carrots, has been reported to modulate immune-related pathways in experimental models; however, the extent to which these observations translate to reduced colorectal cancer risk in humans remains to be determined.

 

Objective: This study investigated whether cultivation methods influence the bioactivity of carrot extracts in an azoxymethane/dextran sodium sulfate (AOM/DSS)-induced murine model of colitis-associated colon tumorigenesis, with emphasis on apoptosis-related markers, inflammatory responses, and gut microbiota alterations.

 

Methods: Six-week-old male C57BL/6 mice (~20 g) were maintained under SPF conditions (12-h light/dark cycle; 23 ± 2 °C; 50 ± 5% humidity). After one week of acclimatisation with ad libitum food and water, mice were randomly allocated to six groups (n = 10/group). The normal and AOM/DSS control groups received saline, whereas the Conventional Fertiliser Carrot (CFC), Seawater Fertiliser Carrot (SFC), Trace Element Fertiliser Carrot (TFC), and Deep-sea Water Mineral fertiliser carrot (NFC) groups received the respective carrot extracts (50 mg/mL). Total phenolic and total flavonoid contents were quantified and analysed using GraphPad Prism 9.4.1.

 

Results: Among the cultivation conditions tested, carrots produced with deep-sea water mineral fertiliser (NFC) were associated with increased expression of apoptosis-related genes and proteins in colon tissue, including p53, p21, Bim, Bad, Bax, Bak, Caspase-9, and Caspase-3. NFC treatment was also associated with lower levels of pro-inflammatory cytokines and mediators (TNF-α, IL-1β, IL-6, IFN-γ, NF-κB, and iNOS) measured across serum, spleen cells, and liver tissues. Gut microbiota profiling indicated a compositional shift in carrot-treated mice relative to controls, including increased relative abundance of taxa previously linked to anti-inflammatory or anti-tumour-associated profiles (e.g., Lachnospiraceae and Mucispirillum schaedleri).

 

Conclusion: In this AOM/DSS mouse model, carrot extracts—particularly those derived from carrots cultivated with deep-sea water mineral fertiliser—were associated with reduced tumour-related endpoints alongside coordinated changes in apoptotic and inflammatory markers and gut microbiota composition. These findings support further investigation into cultivation-dependent differences in carrot bioactivity and encourage additional studies to clarify mechanisms and assess translational relevance in humans.

 

 

Author(s) Details

Yanni Pan
Collaborative Innovation Center for Child Nutrition and Health Development, Chongqing Engineering Research Center of Functional Food, Chongqing Engineering Laboratory for Research and Development of Functional Food, Chongqing University of Education, Chongqing, China.

 

Yeon-Jun Lee
Department of Biotechnology, CHA University, Seongnam, Republic of Korea.

 

Jin Hyeop Kim
Department of Biotechnology, CHA University, Seongnam, Republic of Korea.

 

Min Ji Song
Department of Biotechnology, CHA University, Seongnam, Republic of Korea.

 

KyuBum Kwack

Department of Biomedical Science, CHA University, Seongnam, Republic of Korea.

 

Seung-Hwan Park
Organic Anti-Cancer Agriculture Institute, iCOOP Natural Dream Company, Goesan-gun, Chungcheongbuk-do, Republic of Korea.

 

Sin-Il Sin
Organic Anti-Cancer Agriculture Institute, iCOOP Natural Dream Company, Goesan-gun, Chungcheongbuk-do, Republic of Korea.

 

Ji Hyung Chung
Department of Biotechnology, CHA University, Seongnam, Republic of Korea.

 

Kun-Young Park
Graduate School of Integrative Medicine, CHA University, Seongnam, Republic of Korea.

 

Please see the book here :- https://doi.org/10.9734/bpi/mono/978-81-998509-0-3/CH1

Clinical-pathological Profile of Colorectal Adenocarcinomas with APC, PIK3CA and SMAD4 Mutations in Uganda | Chapter 13 | Medical Research and Its Applications Vol. 5

Introduction: APC gene mutations are an important initiator in tumorigenesis and have been detected in many colorectal cancers (CRC). There is conflicting evidence regarding the association between clinicopathological features of CRC and PIK3CA mutations. A promising prognostic factor of CRC and an important molecule to understand the progression and tumorigenesis of CRC is the SMAD family member 4 (SMAD4). The frequency rates of APC, PIK3CA, and SMAD4 mutations in CRC differ among populations. The objective of this study was to determine the mutation frequencies and determine their association with certain clinicopathological features in Ugandan patients.

Methodology: A cross-sectional study between 2008 to 2021 involving four hospitals in central Uganda and the Department of Pathology, School of Biomedical Sciences, College of Health Sciences, Makerere University. The demographics, stage, grade, LVI status and histopathological subtype were obtained for each CRC participant. The CRC tumours were evaluated using next-generation sequencing (NGS). The pathological mutation rates of APC, PIK3CA and SMAD4 were recorded, along with clinicopathological features. The chi-square test and Fischer’s exact test were used to determine the association between clinicopathological features and mutation status.

Results: Out of 127 CRC participants, the mutation rates were APC: 77(60.6%), PIK3CA: 37(29.1%) and SMAD4: 68(53.5%). A loss of APC was found in 70.2% of female participants compared to 29.8% of female participants with the presence of APC (p=0.047). There were 57% positive APC tumours that were lymphovascular invasion (LVI) positive compared to 42.9% negative APC tumours that were LVI positive (p=0.015). With increasing T-stage, more CRC participants were PIK3CA negative (p=0.018). There was no association between the stage, grade, status, and tumour topography with APC, PIK3CA and SMAD4 mutation status.

Conclusions: In Uganda, the frequency of APC mutations is similar, however, the frequencies of PIK3CA and SMAD4 mutations were higher than that reported in the Western world. APC mutations were associated with a positive LVI status. However, APC, PIK3CA, and SMAD4 mutations were not associated with most clinicopathological parameters.

 

Author(s)details:-

 

Richard Wismayer
Department of Surgery, Masaka Regional Referral Hospital, Masaka, Uganda and Department of Surgery, Faculty of Health Sciences, Equator University for Science and Technology, Masaka, Uganda and Department of Surgery, Faculty of Health Sciences, Habib Medical School, IUIU University, Kampala, Uganda and Department of Pathology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda and Institute of Genetics and Cancer, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK.

Rosie Mathews
Institute of Genetics and Cancer, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK.

 

Celina Whalley
Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.

 

Julius Kiwanuka
Department of Epidemiology and Biostatistics, College of Health Sciences, Makerere University, Kampala, Uganda.

 

Fredrick Elishama Kakembo
Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda and African Centre of Excellence in Bioinformatics and Data Intensive Sciences, Infectious Diseases Institute, Makerere University, Kampala, Uganda.

 

Steve Thorn
Institute of Genetics and Cancer, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK and Department of Oncology, University of Oxford, Oxford, UK.

 

Henry Wabinga
Department of Pathology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda.

 

Michael Odida
Department of Pathology, School of Biomedical Sciences, College of Health Sciences, Makerere University, Kampala, Uganda and Department of Pathology, Faculty of Medicine, Gulu University, Gulu, Uganda.

 

Ian Tomlinson
Institute of Genetics and Cancer, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, UK and Department of Oncology, University of Oxford, Oxford, UK.

 

Please See the book here :- https://doi.org/10.9734/bpi/mria/v5/759