Stevia leaf extract has potential as an anticancer treatment

Stevia may be far more than just a zero-calorie sugar substitute, as it turns out that, when fermented with bacteria isolated from banana leaves, stevia extract is toxic to pancreatic cancer cells. That’s according to a research team at Hiroshima University, who published their findings in the International Journal of Molecular Sciences.

Study co-author Associate Professor Narandalai Danshiitsoodol explained that pancreatic cancer has a five-year survival rate of less than 10%, as the cancer is highly invasive and prone to metastasis — showing significant resistance to existing treatments such as surgery, radiotherapy and chemotherapy. “As such,” he said, “there is an urgent need to identify new and effective anticancer compounds, particularly those derived from medicinal plants.”

Danshiitsoodol noted that prior studies by other researchers demonstrated stevia leaf extract’s potential as an anticancer drug, but isolating and applying the specific bioactive components that protect against cancer cells has remained challenging. However, fermenting with bacteria can structurally change the extract and produce bioactive metabolites, which are compounds that can impact living organisms.

“To enhance the pharmacological efficacy of natural plant extracts, microbial biotransformation has emerged as an effective strategy,” said corresponding author Professor Masanori Sugiyama. Sugiyama’s lab has isolated and evaluated the health benefits of more than 1300 lactic acid bacteria (LAB) 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.”

Specifically, the team fermented stevia leaf extract with plant-derived Lactobacillus plantarum SN13T strain (FSLE) and compared its effects on pancreatic cancer (PANC-1) cells in the lab, alongside non-cancerous human embryonic kidney cells HEK-293, to the effects of non-fermented stevia extract. The cells utilised in these experiments were acquired from established commercial cell lines.

“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.”

Additional analyses identified chlorogenic acid methyl ester (CAME) as the active anticancer compound. When fermented, the concentration of chlorogenic acid in the extract dropped sixfold, indicating a microbial transformation, 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.”

Next, the researchers said they plan to study the effects in a mouse model to better understand the effectiveness of various dosages across a whole-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-tumour agents,” Danshiitsoodol said.

Image credit: iStock.com/AnnekeDeBlok