HONG KONG SAR – Media OutReach – August 7, 2023 – Research by scientists from Hong Kong Baptist University (HKBU) has found that isoliquiritigenin (ISL), a flavonoid isolated from Chinese herbal medicine
licorice, can inhibit the progression of pancreatic cancer. It may also improve the effectiveness of conventional chemotherapy drugs in the treatment of pancreatic cancer. This is the first time that a research group has reported the anti-cancer potential of ISL in the treatment of pancreatic cancer.
A research team led by Dr. Joshua Ko Ka-shun, Associate Professor, Division of Education and Research, HKBU School of Chinese Medicine, found that isoliquiritigenin, a plant extract compound Chinese medicinal licorice, can inhibit the progression of pancreatic cancer.
The research results were published in the international academic journal Phytomedicine and recently presented at the 2023 European Association for Cancer Research Annual Congress in Turin, Italy.
Pancreatic cancer as a “silent killer”
Pancreatic cancer is often called the “silent killer” because most patients have few or no symptoms until it has progressed and spread. According to the World Cancer Statistics 2020 released by the International Agency for Research on Cancer, the mortality to incidence ratio of pancreatic cancer is over 93%. It is the fourth leading cause of cancer death in Hong Kong.
Whipple’s surgery (pancreatic duodenectomy) is the only available cure for pancreatic cancer. However, only 20% of patients are resectable and the recurrence rate is high. In unresectable cases and patients with metastatic pancreatic cancer, the chemotherapy drug gemcitabine (GEM) remains the primary treatment. Nevertheless, GEM-based combination therapy exhibits profound chemoresistance with severe systemic toxicity.
Gancao extract identified as an anti-cancer agent
In the search for alternative treatments for pancreatic cancer, a research team led by
Dr. Joshua Ko Ka ShunAssociate Professor, Teaching and Research Division, School of Chinese Medicine, HKBU, reviewed all potential pancreatic cancer markers and biological therapeutic activities of phytochemicals from the medicinal plant Glycyrrhiza glabra (licorice or Gancao in Chinese) using network pharmacology.
Network pharmacology is an emerging discipline that systematically catalogs the molecular interactions of a drug molecule in a living cell using complex calculations, and has become an important tool in botanical drug discovery. Using this approach, the team identified ISL as a potential anti-cancer agent for the treatment of pancreatic cancer.
With a series of cell experiments, the team demonstrated that ISL suppressed the growth and induced apoptosis (programmed cell death) of pancreatic cancer cells. In two human pancreatic cancer cell lines applied with ISL concentrations of 12.5 μM and 25 μM respectively, their cell survival rates were approximately 50% and 80% lower than those of control cells without ISL applied. The percentage of late stage apoptosis in the two cell lines was 11% and 13% respectively, compared to less than 5% in control cells.
Inhibits cancer progression with fewer side effects
“ISL has a unique property of inhibiting the progression of pancreatic cancer by blocking autophagy, which is a natural process by which cells in the body clean up damaged or unnecessary components. Blocking autophagy at an advanced stage in our experiments causes the cancer cells to die,” says Dr Ko.
The research team further used a mouse tumor model to study the effectiveness of ISL in inhibiting the growth of pancreatic cancer cells.
live. The mice were divided into three groups with GEM (GEM group), ISL (ISL group) and no treatment agent (control group) applied. The ISL group was then divided into two subgroups treated with 30 mg/kg and 60 mg/kg of ISL.
On the 21st day of the experiment, the tumor volumes of the control group and the GEM group were 1000 mm3 and 400mm3 respectively. The tumor volumes of the two ISL subgroups treated with 30mg/kg and 60mg/kg ISL were approximately 500 mm3 and 300mm3 respectively. The results showed that ISL demonstrated treatment effects comparable to those of GEM. Meanwhile, compared to GEM, ISL showed fewer side effects in mice, including neutropenia (lower white blood cell count), anemia and loss of body weight.
Improves the effects of chemotherapy
Current first-line chemotherapeutic drugs for pancreatic cancer, such as GEM and 5-fluorouracil (5-FU), are frequently associated with drug resistance. This is because these drugs induce autophagy which promotes the growth of cancer cells, and thus compromises their therapeutic effects.
To explore the potential of ISL in combating GEM and 5-FU drug resistance, the research team set up experiments with pancreatic cancer cells treated with GEM or 5-FU alone, and GEM or 5-FU with ISL. The growth inhibition rate of pancreatic cancer cells applied with GEM and ISL together is 18% higher than using GEM alone, while the growth inhibition rate with 5- FU and ISL together is 30% higher than 5-FU alone. The results showed that ISL can enhance the therapeutic effects of chemotherapeutic drugs by blocking autophagy, which is conducive to cancer cell death.
“The results of this study open a new avenue for developing ISL as a novel autophagy inhibitor in the treatment of pancreatic cancer. We hope to collaborate with other research partners to further evaluate the efficacy and potential clinical application of ISL in the treatment of pancreatic cancer,” says Dr. Ko.
