Mechanisms of Cancer Chemoprevention by Diet

Project Details


DESCRIPTION (provided by applicant):
Diet is known to play important roles in influencing the development of human
cancer, but the mechanisms are not well understood. The objective of this
planning grant is to organize a multidisciplinary collaborative program to
investigate the molecular mechanisms by which certain dietary constituents
inhibit carcinogenesis. Our collaborative program will consist of
investigators with demonstrated expertise in nutrition, carcinogenesis,
molecular genetics, and signal transduction. We plan to select catechins,
caffeine, and curcumin as the main dietary chemicals for mechanistic
investigations. These compounds occur widely in fruits, beverages, or spices,
and their cancer preventive activities have been demonstrated in animal
models. It would be important to elucidate in depth their mechanisms of action
and to determine whether these mechanisms are relevant in human cancer
prevention. We plan to focus our studies on skin and colon cancers. Well
established animal models and new transgenic mouse models, as well as relevant
cell lines will be used. Our hypothesis is that catechins, caffeine, and
curcumin suppress carcinogenesis by one or more of the following mechanisms:
inhibition of inflammation, cell proliferation, cell transformation, and
angiogenesis, and induction of apoptosis. We will study the key signaling and
metabolic pathways leading to these processes, such as MAP-kinase, AP-1,
Nfr,Kappa B,p53, and arachidonic acid metabolism. We will use DNA microarray
and proteomic approaches to study multiple genetic pathways. A key feature of
our program is to integrate studies in animal models, cell lines, and humans.
Cell line studies will generate hypotheses on possible mechanisms of
chemoprevention, and the hypotheses will be tested in animal models and
humans. It would be important to elucidate the chemopreventive mechanisms most
relevant to humans. We plan to create a structure to facilitate effective
communication and interactions among the collaborators. A web-site is being
set up to pool and share information and research results. We plan to
establish facility Cores to facilitate the research. Monthly meetings and
workshops among the investigators will be scheduled to design strategies and
make study plans for the U54 application.
Effective start/end date9/28/017/31/02


  • National Institutes of Health
  • National Institutes of Health: $169,855.00
  • National Institutes of Health


  • Medicine(all)

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