The findings could lead to affordable, natural cancer treatments for a disease that kills many patients within five years.
A common tea sweetener could offer new hope in the fight against one of the deadliest forms of cancer, according to researchers at Japan's Hiroshima University.
The findings could lead to natural cancer treatments for a disease that kills many patients within five years.
"Globally, the incidence and mortality rates of pancreatic cancer continue to rise, with a five-year survival rate of less than 10%," said co-author Narandalai Danshiitsoodol, associate professor in Department of Probiotic Science for Preventive Medicine, Graduate School of Biomedical and Health Sciences.
"Pancreatic cancer is highly invasive and prone to metastasis, showing significant resistance to existing treatments, such as surgery, radiotherapy and chemotherapy. As such, there is an urgent need to identify new and effective anticancer compounds, particularly those derived from medicinal plants."
Previous research by other scientists had shown stevia leaf extract might work as an anti-cancer drug, but finding and using the specific parts that fight cancer remained difficult, according to Danshiitsoodol. However, using bacteria to ferment the extract can change its structure and create bioactive metabolites -- compounds that affect living things.
The research team used a special bacteria strain called Lactobacillus plantarumSN13T to ferment stevia extract. They then tested how well this fermented version worked against pancreatic cancer cells in laboratory experiments, comparing it to regular stevia extract that wasn't fermented.
"To enhance the pharmacological efficacy of natural plant extracts, microbial biotransformation has emerged as an effective strategy," said corresponding author Masanori Sugiyama, professor in the Department of Probiotic Science for Preventive Medicine, Graduate School of Biomedical and Health Sciences.
His laboratory has studied more than 1,300 different bacteria strains from fruits, vegetables, flowers and medicinal plants. "In this study, we aimed to compare LAB-fermented and non-fermented extracts to identify key compounds that enhance bioactivity, ultimately contributing to the efficacy of herbal medicine in cancer prevention and therapy."
The experiments used established commercial cell lines, testing the fermented stevia extract on pancreatic cancer cells alongside non-cancerous human kidney cells to see how each type responded.
The results showed the fermented extract worked much better than regular stevia extract at killing cancer cells. Most importantly, the fermented version caused little damage to healthy kidney cells, even at high doses, according to Sugiyama.
"Our findings indicate that FSLE demonstrates significantly greater cytotoxicity than the non-fermented extract at equivalent concentrations, suggesting that the fermentation process enhances the bioactivity of the extract," Sugiyama said. "Notably, FSLE exhibited lower toxicity toward the HEK-293 cells, with minimal inhibition observed even at the highest concentration tested."
Further analysis revealed the key cancer-fighting ingredient: chlorogenic acid methyl ester, or CAME. When fermented, the amount of chlorogenic acid in the extract dropped by six times, showing the bacteria had transformed it, according to Danshiitsoodol.
"This microbial transformation was likely due to specific enzymes in the bacteria strain used," Danshiitsoodol said. "Our data demonstrate that CAME exhibits stronger toxicity to cells and pro-apoptotic effects -- which encourage cell death -- on PANC-1 cells compared to chlorogenic acid alone."
The researchers plan to test their findings in mice next to better understand how different doses work in a complete body system.
"The present study has substantially enhanced our understanding of the mechanism of action of the Lactobacillus plantarum SN13T strain in the fermentation of herbal extracts, while also offering a valuable research perspective on the potential application of probiotics as natural anti-tumor agents," Danshiitsoodol said.
Other team members included Rentao Zhang and Masafumi Noda from the Department of Probiotic Science for Preventive Medicine, Graduate School of Biomedical and Health Sciences at Hiroshima University; plus Sayaka Yonezawa and Keishi Kanno from the Department of General Internal Medicine at Hiroshima University Hospital.