The Wargovich Lab
Our laboratory investigates ways to prevent colon cancer. Our focus is on the chemoprevention of cancer, a discipline of cancer research that employs the use of drugs and natural agents to intervene in the process of carcinogenesis before invasive cancer appears. We study cancer biology using a number of human cancer cell lines and also utilize novel animal models for colon cancer.
What We Do
Our laboratory is in the Hollings Cancer Center at the Medical University of South Carolina. We concentrate on the search for natural agents that inhibit the process of chronic inflammation, believed to increase the risk for future cancer. Habitual intake of NSAIDS (Non-steroidal anti-inflammatory drugs) is associated with reduced risk for common forms of cancer, including colon cancer. Because of the toxicity associated with pharmaceutical NSAIDs, we are examining botanical agents that may interfere with chronic inflammation. These include compounds from green tea, the herbal supplements ginkgo and ginseng, and traditional medicines from other cultures.
|We are conducting research to identify cancer prevention agents in traditional medicines used in West Africa. For several years this research has taken us to the West African nation of the Republic of Guinea. One of traditional medicines used there are is the bark of Senegal mahogany (Khaya senegalensis) which appears to inhibit the COX-2 enzyme in human colorectal cell lines studied in the lab.|
Traditional Healer - Kankan, Republic of Guinea,
Other global collaborations include:
|Brazil - in collaboration with Empbrapa Clima Temperado in Pelotas|
|Here we are investigating the Brazilian pitanga fruit (Eugenia uniflora), a fruit native to Brazil that undergoes a ripening process ranging from yellow to orange, and red to purple berries. We hypothesize that this unique chemistry involves carotenoid and anthocyanadin biosynthesis and the fruits should prove to be very high in antioxidant and anti-inflammatory potential – and, possibly very useful in cancer prevention.|
|Colombia - In collaboration with Pontifica Universidad Javeriana -Bogota|
|Our laboratory has begun studies in collaboration with researchers in Bogata on the Colombian native fruits as sources of cancer prevention agents. Fresh fruit from tropical plants is widely consumed in Colombia, and our initial studies are focused on borojo, native Colombian grapes, and starfruit extracts.|
|India - in collaboration with Nisarga Biotech, Sartara|
With Dr. Susan Reed in the College of Dental Medicine at MUSC we are exploring the use of an Ayurvedic herbal formulated in a special mouthwash to alleviate the side effects of radiotherapy to the head and neck region of cancer patients. The mouthwash is designed to reduce the side effects of oral mucositis.
We use supercritical Co2 extracts of the leaves of Azadirachta indica.
Cancer Chemoprevention - Mechanisms
Our studies on green tea polyphenols suggest epigenetic regulation of regulatory genes in colon cancer progression. We are investigating the role of EGCG on the silencing of the RXRα gene in the APCMin+/ mouse, an animal model for colon cancer.
Epigenetic regulation of RXR alpha via inhibition DNMTs and HDACs
Molecular Prevention of Colitis with EGCG and Vitamin D3
The hypothesis underlying this project ties to together the importance of low serum vitamin D levels in colitis patients, our research on RXRα which is silenced in colon cancer, and the VDR. In this project we hypothesize that RXRα may be silenced in colitis due to upregulaton of DNA methyltransferase enzymes (DNMTs). This forecasts that VDR may be impaired due to the silencing of its heterodimer, RXRα. We are using the AOM/DSS model for colitis and testing whether EGCG (which restores RXRα expression) facilitates VDR stimulation by Vitamin D3, causing remission of colitis.
Graduate student Vondina Moseley, postdoctoral fellow, Jay Morris, graduate student Becky Weber, and Mike Wargovich, PhD.
4th Year PhD Student
|Jay Morris, PhD|
Vondina Moseley is currently examining how EGCG regulates gene expression through epigenetic mechanisms involving DNA Methyltransferases and Histone Deacetylases.
Jay Morris is looking at the elucidation of the epigenetic regulation of RXRa by green tea polyphenols.
Becky Weber is investigating colitis and how via EGCG and Vitamin D intervention, the progression from colitis to cancer can be halted through a restoration of the anti-inflammatory pathway regulated by Vitamin D.