Now the trend may be reversing itself again. Recently a number of natural compounds–such as resveratrol from red wine and omega-3 fatty acids from fish oil–have begun to receive close scrutiny because preliminary research suggests they might treat and prevent disease inexpensively with few side effects. Turmeric, an orange-yellow powder from an Asian plant, Curcuma longa, has joined this list. No longer is it just an ingredient in vindaloos and tandooris that, since ancient times, has flavored food and prevented spoilage.
This link between inflammation and the unchecked proliferation of cancer cells prompted Aggarwal to return to his roots. In 1989 he moved to the University of Texas M. D. Anderson Cancer Center and began looking for compounds that might quell inflammation and have an anticancer effect. Remembering from his youth in India that turmeric was an anti-inflammatory in the Ayurvedic literature, he decided to give the spice a try. “We took some from the kitchen and threw it on some cells,” he remembers. “We couldn’t believe it. It completely blocked TNF and NF kappa B.”
Aggarwal has gone on to publish studies showing that blocking the NF kappa B pathway with curcumin inhibits the replication and spread of various types of cancer cells. This work has served as a jumping-off point for early, small clinical trials at M. D. Anderson using curcumin as an adjunct therapy to treat pancreatic cancer and multiple myeloma. Trials are beginning or under way elsewhere for prevention of colon cancer and Alzheimer’s disease, among others. And early cell-based or animal studies have shown that curcumin may act against a range of inflammatory diseases, including pancreatitis, arthritis, inflammatory bowel disease, colitis, gastritis, allergy and fever. It has also shown some promise for diabetes and autoimmune and cardiovascular diseases.
Shaul and his colleagues had found that an anticoagulant, dicoumarol, and related compounds blocked NQO1, which prevented p53 from doing its job. The researchers wondered what would happen if they exposed p53 in normal and myeloid leukemia cells to antioxidants such as curcumin and resveratrol. To their surprise, curcumin, by inhibiting the same enzyme, stopped p53 from sending aberrant cells to the gallows, a finding that was reported in 2005 in the Proceedings of the National Academy of Sciences USA. A few other researchers have published similar results. Aggarwal responds to this body of work by pointing to studies that show the opposite, that curcumin actually activates p53.
AndroScience in San Diego plans to enter the first phase of clinical trials this year with a drug candidate for acne based on compounds derived from curcumin that were discovered in collaboration with the University of North Carolina at Chapel Hill. Similarly, Curry Pharmaceuticals in Research Triangle Park, N.C., is trying to raise financing to move curcumin derivatives from Emory University into clinical trials. But in an age of targeted pharmaceuticals, venture capitalists, leery of side effects, have been hesitant to back new drugs that act on multiple pathways. For his part, Aggarwal, even though he is a co-founder of Curry Pharmaceuticals and holds patents on curcumin, asserts that chemists may have trouble improving on nature: modifying curcumin may only introduce unwanted side effects in patients, he says.
