Doctor Shrikant Anant and his team are researching a natural compound’s effect on reducing the risk of colon cancer in specific high-risk groups.
Familial adenomatous polyposis (FAP) is an inherited condition that carries a nearly 100 percent lifetime risk of developing colon cancer. For people with FAP, the number of polyps increase with age and hundreds to thousands of pre-cancerous polyps can develop in the colon. Similar to a prophylactic mastectomy that individuals with the BRCA1 or BRCA2 gene mutation undergo to reduce their chances of developing breast cancer, people with FAP may have their colon removed, called a colectomy, to reduce their risk of colon cancer.
Mangostin is a major bioactive compound present in mangosteen, a tropical evergreen tree found in India, Myanmar, Sri Lanka and Thailand. Using patient samples containing polyps and tissue from a nearby-unaffected area, Dr. Anant’s team has determined that Mangostin inhibits the growth of FAP patient-derived cells.
However, the mechanism of action is still a question, and the pathway must be identified using an unbiased approach. For this, specific pathways affected in the FAP cells compared to controls must be identified. Then, the team can go back and ask if Mangostin affected those pathways. To identify the pathways, Dr. Anant proposes performing a global sequencing experiment of all the genes expressed in the cells using a technique called RNA-seq.
Researchers will perform this sequencing in multiple isolated patient-derived FAP cells isolated from the polyps and from the matched unaffected region and compare side-by-side. Once sequencing is completed, the team will employ a bioinformatics approach to determine which pathways are affected. With this data, they can return to their original question: i Mangostin affecting these pathways in the cells, as well as in animal models of polyp formation? Once findings are published, the team will apply for NIH funding to advance the next phase of research.