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Herbal extract compound provides potential treatment for pancreatic cancer
7 Aug 2023
Pancreatic cancer, the fourth leading cause of cancer deaths in Hong Kong, is often called the “silent killer” as most patients experience little or no symptoms until it has advanced and spread. According to the Global Cancer Statistics 2020 released by the International Agency for Research on Cancer, the mortality-to-incidence ratio of pancreatic cancer is greater than 93%.
In a new study published in Phytomedicine, a research team led by Dr Joshua Ko Ka-Shun, Associate Professor, Teaching and Research Division of the School of Chinese Medicine, found that a flavonoid isolated from the Chinese herbal medicine licorice can inhibit pancreatic cancer progression. The flavonoid isoliquiritigenin (ISL) may also enhance the efficacy of conventional chemotherapeutic drugs in treating pancreatic cancer. This is the first time that a research group reported the anticancer potential of ISL in treating pancreatic cancer.
Herbal extract identified as anticancer agent
Pancreaticoduodenectomy, also known as the Whipple procedure, is currently the only available curative treatment of pancreatic cancer. However, only 20% of patients are suitable for resection and the recurrence rate is high. In non-resectable cases and metastatic pancreatic cancer patients, the chemotherapeutic drug gemcitabine (GEM) remains the mainstream treatment. Nevertheless, GEM-based combination therapy exhibits profound chemoresistance with serious systemic toxicity.
Using the approach of network pharmacology, Dr Ko and his research team screened all the potential pancreatic cancer disease markers and the biological therapeutic activities of phytochemicals from the medicinal plant Glycyrrhiza glabra (licorice, or Gancao in Chinese). They identified ISL as a potential anticancer agent for the treatment of pancreatic cancer.
Through a series of cell experiments, the team demonstrated that ISL suppressed the growth and induced apoptosis (programmed cell death) of pancreatic cancer cells. “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,” says Dr Ko.
The research team further employed a mice tumor model to investigate the efficacy of ISL in inhibiting pancreatic cancer cell growth in vivo. 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 further divided into two sub-groups treated with 30mg/kg and 60mg/kg of ISL respectively.
On the 21st day of the experiment, the tumor volumes of the control group and the GEM group were 1000 mm3 and 400 mm3 respectively. The tumor volumes of the two ISL sub-groups treated with 30mg/kg and 60mg/kg of ISL were about 500 mm3 and 300 mm3 respectively. The results showed that ISL demonstrated treatment effects comparable to that of GEM. Meanwhile, compared with GEM, ISL showed fewer side effects in mice including neutropenia (drop in white blood cell count), anemia and body weight loss.
Enhances effects of chemotherapies
Current first-line chemotherapeutic drugs for pancreatic cancer, such as GEM and 5-fluorouracil (5-FU), are frequently associated with chemoresistance. It is because these drugs induce autophagy which favours the growth of cancer cells, and thus jeopardises their treatment effects.
To explore ISL’s potential in counteracting the chemoresistance of GEM and 5-FU, the research team set up experiments with pancreatic cancer cells treated with GEM or 5-FU alone, and GEM or 5-FU together with ISL. The growth inhibition rate of pancreatic cancer cells applied with both GEM and ISL is 18% higher than using GEM alone, while the growth inhibition rate using both 5-FU and ISL is 30% higher than that of 5-FU alone. The results showed that ISL can enhance the treatment effects of chemotherapeutic drugs by blocking autophagy, which is conducive to the death of cancer cells.
“The findings in 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 effectiveness and potential clinical application of ISL in treating pancreatic cancer,” says Dr Ko.