The first step in tumor metastasis is the invasion or migration of cancer cells into surrounding tissue. This movement is triggered by chemical signals from their environment and facilitated by the activity of the cell membrane and its attachment to the extracellular matrix -- a three-dimensional network of large molecules that gives structural support to cells. Another way by which cancer spreads is via the blood vessels. Called intravasation, this process involves the entry of cancer cells into the blood or lymph vessels. This allows cancer cells to reach tissue located far away from their site of origin. Intravasation is considered a relatively late event in tumor development.
According to previous studies, carnosine has the ability to regulate the migration and invasion of human colorectal cancer (CRC) cells. However, the mechanism by which it achieves this is still unknown. To address this, the researchers treated cultured HCT-116 cells (human colon cancer cell line) with carnosine, then examined their migratory and intravasive abilities. The researchers also looked at the expression of EMT-associated molecules and matrix metalloproteinases (MMPs) after carnosine treatment. MMPs are enzymes that promote cancer progression by increasing cancer cell growth, migration, invasion, metastasis and angiogenesis -- the development of new blood vessels.
The researchers reported that carnosine treatment inhibited both migration and invasion of treated cells. It also significantly decreased the expression of Twist-1, a protein that promotes tumor cell invasion and metastasis. Meanwhile, carnosine increased the expression of E-cadherin, a cell adhesion molecule and known tumor suppressor. Loss of E-cadherin-mediated adhesion turns benign cells into invasive, metastatic cancer cells. The researchers also detected increases in the mRNA and protein levels of TIMP-1 after carnosine treatment. TIMP-1 is a tissue inhibitor of MMPs.
Besides suppressing pro-metastatic components, treatment with carnosine also reduced the levels of phosphorylated IkB and NF-kB DNA-binding activity in HCT-116 cells. IkB is a protein involved in the activation of NF-kB, a transcription factor that plays an important role in inflammation, immunity, cell proliferation and apoptosis.
Based on these findings, the researchers concluded that carnosine inhibits the migration and intravasation of CRC cells by suppressing NF-kB activity and modulating MMP and EMT-related gene expression.
The body naturally produces the dipeptide carnosine. It is formed by the linking of two amino acids, namely, alanine and histidine. An endogenous molecule with antioxidant properties, carnosine is mainly found in skeletal muscles and in the brain. Humans also obtain it from dietary sources like beef, fish and chicken meat or by taking carnosine supplements. (Related: Carnosine provides broad-range cellular protection to fight vascular injury and extend lifespan.)
According to research, carnosine can boost the immune system, support eye health and improve a person's mood and brain function. Carnosine supplements are said to be a great remedy for a variety of conditions, such as autism, cataracts, diabetic complications, high blood pressure and kidney problems. Clinical evidence also suggests that carnosine can prevent cognitive decline, slow down the progression of Alzheimer's disease, protect against diabetes and help fight cancer.
Read more stories about carnitine and other anti-cancer supplements at SupplementsReport.com.