Research

Exploring mechanisms of diet-colon cancer associations through candidate molecular interaction networks

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Abstract

Background: Epidemiological studies in the recent years have investigated the relationship between dietary habits and disease risk demonstrating that diet has a direct effect on public health. Especially plant-based diets-fruits, vegetables and herbs-are known as a source of molecules with pharmacological properties for treatment of several malignancies. Unquestionably, for developing specific intervention strategies to reduce cancer risk there is a need for a more extensive and holistic examination of the dietary components for exploring the mechanisms of action and understanding the nutrient-nutrient interactions. Here, we used colon cancer as a proof-of-concept for understanding key regulatory sites of diet on the disease pathway. Results: We started from a unique vantage point by having a database of 158 plants positively associated to colon cancer reduction and their molecular composition (similar to 3,500 unique compounds). We generated a comprehensive picture of the interaction profile of these edible and non-edible plants with a predefined candidate colon cancer target space consisting of similar to 1,900 proteins. This knowledge allowed us to study systematically the key components in colon cancer that are targeted synergistically by phytochemicals and identify statistically significant and highly correlated protein networks that could be perturbed by dietary habits. Conclusion: We propose here a framework for interrogating the critical targets in colon cancer processes and identifying plant-based dietary interventions as important modifiers using a systems chemical biology approach. Our methodology for better delineating prevention of colon cancer by nutritional interventions relies heavily on the availability of information about the small molecule constituents of our diet and it can be expanded to any other disease class that previous evidence has linked to lifestyle.

dietray pattern disease pathway drug discovery molecular interaction network colon cancer Colonic Neoplasms (MeSH) digestive system disease neoplastic disease pathology diet therapy genetics prevention and control etiology Plantae (Plants) - Plantae [11000] plant common medicinal plant Primates Mammalia Vertebrata Chordata Animalia (Animals Chordates Humans Mammals Primates Vertebrates) - Hominidae [86215] human common Rodentia Mammalia Vertebrata Chordata Animalia (Animals Chordates Mammals Nonhuman Vertebrates Nonhuman Mammals Rodents Vertebrates) - Muridae [86375] Rattus norvegicus species Mus musculus species gene phytochemical protein network 03502 Genetics - General 03504 Genetics - Plant 03506 Genetics - Animal 03508 Genetics - Human 12502 Pathology - General 12512 Pathology - Therapy 13202 Nutrition - General studies nutritional status and methods 14006 Digestive system - Pathology 24004 Neoplasms - Pathology clinical aspects and systemic effects 51504 Plant physiology - Nutrition 54000 Pharmacognosy and pharmaceutical botany Biochemistry and Molecular Biophysics Human Medicine Medical Sciences Pharmacology chemoinformatics method mathematical and computer techniques Gastroenterology Molecular Genetics Nutrition Oncology Pharmacognosy BIOTECHNOLOGY GENETICS COLORECTAL-CANCER INTEGRATION PREVENTION PREDICTION METABOLISM