Veterans Affairs

Bowel anti-inflammatory and colorectal cancer therapeutic

Tri-peptide KPV represents a promising drug targeting PepT1, a transporter involved in inflammation and tumorigenesis

Medical & Biotechnology

The Department of Veterans Affairs is making its research available to health care companies that would develop it into new products and services.

Colon cancer cells. Flickr

The proton-coupled oligopeptide transporter (POT) family includes four transporter proteins (PepT1, PepT2, PhT1, PhT2)  involved in the intake of small peptides into cells along with a proton. PepT1 is a di- and tri-peptide transporter that is primarily expressed in the small intestine in healthy individuals. PepT1 transports these specific peptides, but not single amino acids or peptides with more than three amino acids. Under normal physiological conditions, intestinal epithelial cells express PepT1, which aids in the transport and absorption of di- and tripeptides from endogenous sources into the intestinal cells.

During chronic inflammation, the expression profile of PepT1 within the gastrointestinal tract is altered. In patients with chronic diseases such as inflammatory bowel disease (IBD) and short bowel syndrome, PepT1 expression is upregulated in the colon. Chronic intestinal inflammation, left untreated, can become colorectal cancer (sometimes referred to as colitis-associated cancer or CAC) – one of the most common human malignancies.

VA-funded scientists have developed a treatment regime for colorectal cancer and IBD composed of an anti-inflammatory tri-peptide (Lys-Pro-Val or KPV) that targets PepT1. This particular tri-peptide, which is derived from alpha-melanocyte-stimulating hormone, has been shown to have anti-inflammatory properties and to effectively reduce chemically induced colitis in mice.

Given that KPV is able to decrease the tumor number and the proliferation of malignant colonic epithelial cells in a PepT1-dependent way in an animal model, researchers believe it is worth further consideration that PepT1 can be a therapeutic target for the treatment of colonic inflammation and subsequent tumorigenesis.

Do you have questions or need more information on a specific technology? Let's talk.

Contact Us