Indirubin

Indirubin

INDIRUBIN
Traditional Chinese Medicine compound helps combat cancer.

For over 4,000 years, practitioners of Traditional Chinese Medicine (TCM) have amassed a natural pharmacopoeia that is, for the most part, still in use in China and other parts of the world. A pharmacopoeia is a book containing information on therapeutic agents, standards for their strength and purity, and what they contain. Some of these natural sources (usually plants) are described as capable of relieving cancer. Although the TCM definition of cancer may differ from that of modern science, several Chinese plants do have significant antitumor activity.

It has been the custom to treat chronic myelocytic leukemia (CML) with a traditional herbal mixture, Danggui Longhui Wan. Leukemia is a progressive proliferation of abnormal leukocytes (white blood cells). It is a cancer of the bone marrow, the place where blood cells are formed. In chronic leukemia, there is a gradual onset of symptoms of anemia and marked enlargement of the spleen, liver, or lymph nodes due to overproduction of the leukocytes. Leukemia is named according to the main cell type that is affected. CGL, also called chronic granulocytic leukemia, affects granulocytes, another type of leukocyte. Myelocytic refers to young cells of the granulocytic series, occurring normally in the bone marrow.

In 1966, the Institute of Haematology of the Chinese Academy of Medical Sciences identified the active factor in Danggui Longhui Wan, a complex mixture of 11 herbs. Antitumor activity was traced to one ingredient, Qing Dai (Indigo naturalis). This dark blue powder could be isolated from the leaves of Baphicacanthus cusia, Polygonium tinctorium, Isatis indigotica, Indigofera suffrutticosa, and Indigofera tinctoria. The powder contained a high level of the blue dye, indigo. Researchers at the University of Kaiserslautern in Germany, led by Ralph Hoessel, continued the early research and traced the antileukemic activity to the red-colored component, indirubin, which was a minor part of the mixture. These results were recently published in the journal Nature Cell Biology.

In experiments on human cancerous cells and in rats with sarcoma (a connective tissue cancer) indirubin was found to inhibit DNA synthesis. By doing so, cancerous cells were prevented from dividing and producing more cancer cells. The animal studies showed that indirubin had low toxicity; there were no effects on bone marrow or production of blood cells as seen with many anticancer drugs.

In addition to CML, indirubin has been approved for clinical trials against CGL. In one study, 26 percent of 314 CGL patients showed complete remission and 33 percent showed partial remission when given indirubin treatment. Toxicity was low and side effects included mild stomach pain, diarrhea, nausea, and vomiting. When indirubin was compared to busulfan (a drug for treating cancer) in CGL patients, there was similar efficiency in producing remission, although the drug had a higher rate of complete remissions. Nevertheless, use of busulfan increases susceptibility to infection and can cause blood problems.

Indirubin works to stop the uncontrolled growth of tumor cells by inactivating enzymes called cyclin-dependent kinases (CDKs). These enzymes regulate cell division. In non-cancerous cells these enzymes normally turn off at an appropriate time. In cancerous cells they stay activated and the cells keep dividing uncontrollably. Indirubin can bind to CDKs, block their activity, and halt the wild cell division.

Indirubin and similar compounds belong to a class of substances called indigoids. Natural indigoids can be obtained by fermenting indigo-producing plants, of which there are several hundred species in a wide range of plant families, and are also found in Muricidae and Thaididae mollusks. The researchers are looking forward to investigating these various sources with the hope of isolating new and more effective indigoids useful in combating cancer.
REFERENCES
Hoessel, R., Leclerc, S., Endicott, J.A., et al. "Indirubin, the active constituent of a Chinese antileukaemia medicine, inhibits cyclin-dependent kinases," Nature Cell Biology 1(1):60-67, May 1999.
~~~~~~~~
By Jean Barilla, M.S.

Share this with your friends