From The May 1997 Issue of Nutrition Science News
Modified Citrus Pectin May Halt Metastasis
by Stephanie Briggs, Ph.D.
Pectin, a compound derived from citrus fruits, may provide a safe means of reducing or preventing the spread of cancer. Pectin is a branched-chain carbohydrate found in plant cell walls that holds adjacent cells together. All plants contain pectin, but apples and citrus fruits are particularly rich in these large molecules. Modified citrus pectin (MCP) is made by breaking the large pectin molecules into shorter and less-branched chains and partially degrading the carbohydrates.
Special proteins called "lectins" occur on cell surfaces and are used to communicate with other cells. Cells interact when their lectins combine with structurally complementary forms on other cells. There are many kinds of lectins. One particular family of lectins has an affinity for galactose, and hence are called galectins. Certain cancer cells are especially rich in galectins 1 and interact with other cells by bonding to galactose. By this means, a cancer cell that detaches from a primary tumor and enters the blood or lymphatic circulation can attach to a vascular endothelial cell far away from the primary site and begin a new daughter tumor. This is the process of metastasis. MCP has particularly high amounts of the sugar galactose, which may be responsible for its ability to greatly reduce metastasis in animals.
Interfering With Cancer
By virtue of its large amount of galactose, it is thought that MCP attaches to free cancer cells and makes it impossible for them to interact with blood vessel cells and start new tumors. The evidence of MCP's metastasis prevention comes from animal experiments, supported by in vitro studies with human cancer cell lines. Its effectiveness against metastasis of human cancers, however, remains to be established. W. Marston Lineham, M.D., of the National Institutes of Health, acknowledges the potential for this type of research on MCP.2
An encouraging study published in the Journal of the National Cancer Institute showed that treating melanoma cells with MCP prevented their ability to form new tumors.3 Melanoma cells were grown in culture and incubated with either no additions or with MCP. The melanoma cells were injected into the tail veins of mice. After 17 days, the mice were autopsied and the number of tumors in their lungs (the site of metastasis) was counted. The group receiving cells incubated with no additions averaged 33 lung tumor colonies per mouse. Mice receiving MCP-treated melanoma cells had no lung tumors. This suggested that MCP had covered up the melanoma cells' binding sites, making them unable to attach to other cells.
While this study is encouraging, it doesn't show how to apply the principle in an animal that already has cancer. Since a detached cancer cell is most likely to encounter MCP in the bloodstream, the next step was testing the effect of orally delivered MCP.
First, rats were injected with prostate cancer cells.4 Based on previous research, tumor formation was expected within 30 days. From day four after injection until killing the animals at day 30, rats were divided into four groups. One group was the control and was given no additional supplementation. The other three groups were given different concentrations of MCP in their drinking water: 0.01 percent, 0.1 percent or 1 percent. In the control group, cancer cells had metastasized in the lungs of 15 out of 16 rats, with an average of nine tumors per rat. While the group given .01 percent MCP solution had similar results, there were significantly fewer metastases in the 0.1 percent group (fewer rats affected and fewer tumors per rat) and fewer still in the 1 percent group. In fact, the average number of tumors per rat in the 1 percent group was one.
Oral consumption of MCP, then, can reduce metastasis in rats injected with prostate cancer cells. But will oral consumption of MCP by humans have the same effect on metastasis of human cancers? Some preliminary studies suggest that possibility. Human cancer cell lines--including prostate adenocarcinoma cells, breast carcinoma cells, melanoma cells and laryngeal epidermoid carcinoma cells--treated with MCP showed greatly reduced adhesion to an endothelial base in vitro.5 It apparently bound sites on the cancer cells that otherwise might have attached to blood vessel cells.
But can MCP pass through the digestive process and enter the blood? The usual teaching is that carbohydrates are broken down to their simple sugars before absorption. Were free galactose units from digested pectin responsible for the protective effect observed in the rat study, or were the MCP molecules themselves absorbed? Whether a molecule is absorbed depends in part on its size.
Not all MCPs are alike. According to the method of their manufacture, they can differ in molecular size, degree of methylation of their side chains, and pH. Although rat and human digestion are not exactly alike, there are enough similarities to make some general conclusions. Until we know more, it seems logical that the MCP for human consumption should fit the profile of what worked with rats.
The MCP found effective in rats that received MCP in their drinking water met particular specifications: molecular fragments of about 10 kilodaltons, no more than 10 percent methylation, and a 6.3 pH. The molecular size must be small enough to be absorbed, yet large enough to fulfill its binding function. Some marketed MCPs have molecular sizes greater than 34,000 kilodaltons or smaller than 8,000. The degree of methylation determines the number of available binding sites--the more methylation, the fewer the free binding sites. Some commercially available MCPs have 50 percent to 70 percent methylation. Its pH can also change the properties and functions of pectin--near neutral is thought to be optimal, although some available pectins have a pH less than 3.2 or higher than 7.
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