Study Shows Chemical in Licorice Fights Pancreatic Cancer

Scientists recently published findings that a flavonoid in licorice root can inhibit the progression of pancreatic cancer.

Dried sticks of licorice root. New Africa/Shutterstock

Think licorice and you probably imagine a chewy black rope with a unique sweet flavor. If you get a traditional recipe of this humble confection, it may even contain a cancer-killing chemical.

Scientists from Hong Kong Baptist University (HKBU) recently published findings that a flavonoid in licorice root can inhibit the progression of pancreatic cancer. Researchers showed that this same licorice-based chemical may also enhance the efficacy of chemotherapy drugs used to treat pancreatic cancer.

The research was published in the international academic journal Phytomedicine and presented at the Annual Congress of the European Association for Cancer Research 2023 in Torino, Italy.

The findings are important because pancreatic cancer has characteristics that make it potentially more devastating than other cancers. It’s aggressive and has a high mortality rate. According to Global Cancer Statistics 2020, a report released by the American Cancer Society and the International Agency for Research on Cancer, the mortality-to-incidence ratio of pancreatic cancer is greater than 93 percent.

The World Health Organization estimated pancreatic cancer as the third-leading cancer-related cause of death in people of all ages in the United States and several European countries.

It’s a vicious cancer that can strike without any clear warning. Patients typically experience little or no symptoms with pancreatic cancer—until it has considerably progressed. When doctors do finally catch it, the disease is very advanced and has spread to other organs.

When most any cancer is caught early enough, a surgeon may be able to remove it. But by the time a patient receives a pancreatic cancer diagnosis, surgical removal is usually no longer an option. Only about 20 percent of pancreatic cancer patients are eligible for surgery (known as a Whipple operation or pancreaticoduodenectomy).

For those who make the cut, the recurrence rate of cancer is high. Long-term complications from the Whipple procedure (which include pancreatitis, hernia, ulcer, and bowel obstruction) occur in nearly a third of cases, and nearly one-fifth of all procedures require re-intervention.

The typical treatment for pancreatic cancer is chemotherapy. Serious side effects are common.

Licorice’s Healing Legacy

These are the realities that a pancreatic cancer patient must face. So why would HKBU scientists study licorice as a source of medicine for such a daunting disease? In part, because of its traditional use. Licorice root has been used as a medicine around the world since ancient times.

In China, licorice root is known as gan cao (which means “sweet herb”) and has been used for a number of health conditions for millennia. Because of its sweet flavor and a long-held reputation for harmonizing combinations of other herbs, licorice is found in a vast array of traditional Chinese herbal formulas.

Licorice root has long been used in the West as well, for treating gastrointestinal, respiratory, and inflammatory diseases. Modern science continues to validate the root’s healing potential.

A meta-analysis of the anti-inflammatory actions of licorice, published in a 2017 edition of the journal Pharmaceutical Biology, determined that several compounds in the root “exhibit evident anti-inflammatory properties.”

In an analysis published in 2020, licorice was found to nurture health in several ways, including supporting hormonal balance and having antibacterial, antiviral, expectorant, anti-cancer, and other properties.

Understanding ISL

When modern science analyzes a plant’s healing power and potential, it isolates the chemicals it contains. Licorice root contains several chemicals with medicinal properties. A saponin called glycyrrhizin is the best-known and most frequently studied of these chemicals, but many others remain. The licorice compound at the heart of the HKBU study is known as isoliquiritigenin (ISL).

HKBU researchers already knew when going into their project that ISL had properties that might address some of the trademarks of pancreatic cancer. It’s an antioxidant that has previously been shown to address things such as oxidative stress and metabolic malfunction.

The research team was led by Joshua Ko Ka-Shun, who holds a doctorate in pharmacology and is an associate professor at the teaching and research division of the School of Chinese Medicine at HKBU. Mr. Ko’s team began the project by separating out all the other licorice root phytochemicals to focus exclusively on ISL’s cancer-fighting effect.

The team conducted a series of cell experiments to demonstrate that ISL suppressed the growth of pancreatic cancer cells, thereby inhibiting cancer progression.

“ISL possesses a unique property of inhibiting pancreatic cancer progression through the blockade of autophagy, which is a natural process where the body’s cells clean out damaged or unnecessary components. The blockade of late-stage autophagy in our experiments results in cancer cell death,” Mr. Ko said in a statement.

Researchers also looked at tumors in mice to investigate the efficacy of ISL in inhibiting pancreatic cancer cell growth. Mice were divided into groups in which some received chemotherapy with gemcitabine (GEM), a common treatment for pancreatic cancer. Other mice received doses of ISL.

ISL demonstrated treatment effects that were found to be comparable to that of GEM but without the GEM side effects, such as anemia, a drop in white blood cells, and weight loss.

Although GEM (and 5-fluorouracil) are typically the standard of care when it comes to pancreatic cancer, these drugs are frequently met with chemoresistance, which means the cancer is able to evade the treatment. Instead of killing the cancer as intended, these chemo drugs can encourage the growth of cancer cells.

Mr. Ko and his team examined how ISL might help in counteracting chemoresistance. Researchers looked at pancreatic cancer cells treated with chemo drugs alone, compared to cells where the drugs were used in tandem with ISL. They found that ISL combined with GEM inhibited the growth of pancreatic cancer cells 18 percent more compared to the group treated with GEM alone.

ISL combined with 5-fluorouracil was 30 percent more effective than chemo by itself.

Researchers concluded that ISL could considerably enhance conventional treatment.

“The findings in this study open a new avenue for developing ISL as a novel autophagy inhibitor in the treatment of pancreatic cancer,“ Mr. Ko said. ”We hope to collaborate with other research partners to further evaluate the effectiveness and potential clinical application of ISL in treating pancreatic cancer.”