We have been interested in the study of human
cancer prevention, particularly in human colorectal cancer. Specifically, we seek to determine the anti-cancer effects of the following:
There are several
known cancer chemopreventive compounds, but non-steroidal anti-inflammatory
drugs (NSAIDs) including aspirin, ibuprofen, naproxen, etc., are the most well
determined chemopreventive compounds in colorectal cancer. Many potential
molecular mechanisms are proposed regarding their effects on
anti-tumorigenesis, but apoptosis induction by these compounds is one mechanism
to exert their anti-tumorigenic activity. We have found that NSAIDs induce
several pro-apoptotic proteins, including NAG-1, ATF3, EGR-1, and other tumor
suppressor proteins at the transcriptional level, and these proteins play
pivotal roles in NSAID-induced anti-tumorigenesis.
The second group of chemopreventive compounds we have been interested in is PPARgamma ligands.
These compounds are in use in clinics as anti-diabetic drugs; however, it has
also been shown that these drugs have an anti-cancer activity. PPARgamma ligands increase the expression of
NAG-1, EGR-1, and other tumor suppressor proteins in a PPARgamma-independent
The third compounds we are interested in are polyphenols found in our
meals. Many food components – from grapes, soybeans, green tea, cabbage, and
broccoli – possess anti-cancer activity. Epidemiological studies have
suggested that nutrition plays an important role in carcinogenesis, and dietary
factors have been estimated to account for up to 80% of cancers of the
gastrointestinal tract. Approximately 30% of cancer morbidity and mortality
might be prevented with proper adjustment of diets. We have found that several
polyphenols increase tumor suppressor proteins at the transcriptional level.
We are expanding our research to other cancers such as prostate, breast, lung,
and head and neck cancers, and our research will provide better rationale
for use in designing cancer chemopreventive compounds in the future.