Pancreatic Cancer Cells Killed by Traditional Herbal Compound

An herb used in traditional medicine by many Middle Eastern countries may help combat pancreatic cancer, one of the most difficult cancers to treat. Researchers have found that thymoquinone, an extract of Nigella sativa seed oil, blocked pancreatic cancer cell growth and destroyed the cells by enhancing the process of programmed cell death.

While the studies are in the early stages, the findings suggest that thymoquinone could eventually have some use as a preventative strategy in patients who have gone through surgery and chemotherapy or in individuals who are at a high risk of developing cancer.

According to Hwyda Arafat, M.D., Ph.D., associate professor of surgery at Jefferson Medical College of Thomas Jefferson University (Philadelphia, PA, USA), N. sativa helps treat a wide range of diseases, including some immune and inflammatory disorders. Earlier studies also have shown anticancer activity in prostate and colon cancers, as well as antioxidant and anti-inflammatory effects.

Using a human pancreatic-cancer cell line, Dr. Arafat and her team demonstrated that thymoquinone killed approximately 80% of the cancer cells. They found that thymoquinone triggered apoptosis, and that a number of important genes, including p53, Bax, bcl-2, and p21, were affected. The researchers discovered that expression of p53, a tumor-suppressor gene, and Bax, a gene that promotes programmed cell death, was increased, while bcl-2, which blocks such cell death, was decreased. The p21 gene, which is involved in the regulation of different phases of the cell cycle, was considerably increased. The researcher presented her findings in May 2008 at the Digestive Disease Week in San Diego, CA, USA.

Dr. Arafat and her co-workers also found that thymoquinone caused epigenetic changes in pancreatic cancer cells, modifying the cells' DNA. She reported that these changes involve adding acetyl groups to the DNA structure, specifically to blocks of proteins called histones. This acetylating process can be important for genes to be read and converted into proteins. In this instance, it could involve the genes that are key to initiating programmed cell death. "We looked at the status of the histones and found surprisingly that thymoquinone increased the acetylation process,” Dr. Arafat stated. "We never anticipated that.”

At the same time, adding thymoquinone to pancreatic cancer cells reduced the production and activity of enzymes called histone deacetylases (HDACs), which remove the acetyl groups from the histone proteins, stopping the gene transcription process. Dr. Arafat noted that HDAC inhibitors are a "hot” new class of drugs that interfere with the function of histone deacetylases, and is being studied as a treatment for cancer and neurodegenerative diseases. Finding that thymoquinone functions as an HDAC inhibitor, she reported, "was very remarkable and really exciting.”

Pancreatic cancer, the fourth-leading cause of cancer death in the United States alone, takes approximately 34,000 lives per year. The disease frequently is detected after it has metastasized and only 4% of individuals with pancreatic cancer live for five years after diagnosis.


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