Researchers at the Wayne State University School of Medicine and the Barbara Ann Karmanos Cancer Institute are taking a more holistic view of treatment for colorectal cancer, exploring the beneficial properties of curcumin, the major active ingredient in the spice turmeric.

Besides being a natural compound used in Southeast Asian dishes, turmeric has been used for centuries as an anti-inflammatory agent. School of Medicine and Karmanos researchers have been exploring the mechanical and therapeutic functions of curcumin for about seven years and have published a recent research paper titled “Elimination of Colon Cancer Stem-like Cells by the Combination of Curcumin and FOLFOX” in the December issue of scientific journal Translational Oncology. The paper highlights the scientists’ findings that using curcumin alone or paired with FOLFOX (a standard chemotherapy agent) in treating chemotherapy-resistant colon cancer cells resulted in a marked reduction in cancer stem-like cells.

“What we are interested in doing is utilizing natural agents to supplement or enhance the effectiveness of chemotherapeutic drugs,” said Adhip Majumdar, Ph.D., professor of Internal Medicine at the School of Medicine and the Karmanos Cancer Institute, and senior research career scientist at the Veterans Administration Medical Center. Dr. Majumdar is the corresponding author of the paper and the study’s principal investigator.

“I think this is very pioneering work because it further explores what we feel is an effective partnership between natural agents and traditional chemotherapy methods,” he said. “It’s a very hot area of work. We wanted to get the research out as fast as possible so that more in-depth research can continue.”

Cancer stem-like cells are resistant to conventional chemotherapy and can renew themselves. They can also develop into any cell in the overall tumor population and drive continued expansion of malignant cells, allowing them to invade and metastasize. Scientists believe failure to eliminate cancer stem-like cells is one of the underlying causes for continued malignancy. Once colorectal cancer returns, it is even harder to treat.

“Surgery is probably the best treatment that we have in fighting colorectal cancer,” said study co-author Bhaumik B. Patel, M.D., assistant professor of Internal Medicine and Oncology at the School of Medicine and the Karmanos Cancer Institute, and staff oncologist at the Veterans Administration Medical Center. “If cancer stem cells haven’t gone into the blood stream and we can remove the entire tumor, then we can remove the stem cells.

“We now need to address that population of colorectal cancer patients whose stem cells have gone into the blood with better treatments that are less toxic.”

Colorectal cancer is the third most common cancer in men and women, constituting 10 percent of new cancer cases in men and 11 percent in women each year. The American Cancer Society estimates that almost 78,000 men and almost 75,000 women will be diagnosed with colorectal cancer this year. Even though surgery can be effective in treating isolated cancer cases when paired with chemotherapy, nearly 50 percent of patients with colorectal cancer redevelop the disease.

Curcumin, unlike standard chemotherapy agents, has no toxicity for the patient.

The researchers are attempting to improve how curcumin can be absorbed into the blood and other tissue and can reach cancer cells to kill them. Curcumin has good absorption rates in the gastrointestinal tract but very low absorption rates in the blood, where it could serve to help eradicate cancer stem cells if the cancer has metastasized.

“Despite its low absorption, it accumulates in the intestinal mucosa,” said Fazlul Sarkar, Ph.D., professor of Pathology for the School of Medicine and the Karmanos Cancer Institute. Dr. Sarkar is co-author of the study. “It also goes into the circulation quickly. Within half an hour to an hour, it peaks in the blood and then it disappears. To have a biological effect other than in the colon, one needs to improve the bio-availability of curcumin.”

This type of research is continuing in Dr. Sarkar’s laboratory, as documented by his publications that describe the increased synthesis of the new curcumin compound the researchers have created, compared to curcumin in its natural state. Dr. Sarkar believes that utilizing natural agents and perhaps their corresponding synthetic compounds should be paired with other methods of killing cancer cells.

“You need to take a holistic approach toward medicine. Food is the only way to make people healthy,” he said. “Using a natural agent like curcumin, it will inhibit all the inflammation that goes on in your entire system as you age. It synergizes drug-resistant cancer cells to the conventional drug, allowing the drug to work effectively in killing those cells.”

Fellow study authors include Yingjie Yu, M.D., assistant research professor of medicine at the School of Medicine; Shailender S. Kanwar, Ph.D., of the Department of Internal Medicine at the School of Medicine; and Jyoti Nautiyal, Ph.D., of the departments of Internal Medicine and Pathology at the School of Medicine and the Karmanos Cancer Institute.

The scientists said they hope their work, which was performed on human cancer cells in the laboratory, inspires continued research into how natural compounds can help the cancer treatment process overall, whether it is for colon cancer or breast, pancreas, prostate, and head and neck cancers. The results with curcumin specifically have been so promising in the laboratory, researchers have already tested it in Phase I and Phase II trials.

“Research has to move on from here,” Dr. Sarkar said. “Researchers are trying to make improvements on the curcumin molecule so that we have different synthetic compounds, which would be useful for killing most cancer cells, especially cancer stem-like cells.”