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Natural sweetener Stevia found safe and effective at killing pancreatic cancer cells

Stevia Fermentation Unleashes Potent Pancreatic Cancer Fighter

Nature’s Sweetener Transformed into Promising Therapeutic Agent

Pancreatic cancer remains a formidable challenge, with a stark five-year survival rate below 10%. Researchers are now exploring natural avenues, with a fermented stevia extract showing remarkable potential in lab studies.

Unlocking Nature’s Potential

The stevia plant, renowned for its sweetening properties, also harbors bioactive compounds with suspected antioxidant and anticancer benefits. While purified stevia compounds have demonstrated some anti-tumor effects, whole leaf extracts have yielded only modest results, often requiring very high concentrations to impact cancer cell growth.

Boosting Efficacy Through Bacterial Power

Microbial fermentation is emerging as a key strategy to enhance the potency of natural compounds. Lactic acid bacteria (LAB), known for their health benefits, can transform plant extracts into more effective agents. Scientists at Hiroshima University focused on *Lactobacillus plantarum* SN13T, a strain found on banana leaves, to investigate its impact on stevia leaf extract.

The research, published in the *International Journal of Molecular Sciences*, aimed to determine if fermenting stevia leaf extract with this bacterial strain could amplify its anticancer properties.

Striking Results in Lab Tests

The team developed a fermented stevia leaf extract (FSLE) and tested it against pancreatic cancer cells (PANC-1) and healthy kidney cells (HEK-293). The fermented version proved significantly more effective.

“FSLE demonstrates significantly greater cytotoxicity than the non-fermented extract at equivalent concentrations. Notably, FSLE exhibited lower toxicity toward the HEK-293 cells, with minimal inhibition observed even at the highest concentration tested.”

Masanori Sugiyama, Professor, Hiroshima University

This selective toxicity—killing cancer cells while sparing healthy ones—is a critical advancement. Further tests revealed FSLE halted cancer cell proliferation and migration, indicating a strong anti-proliferative effect.

The impact of FSLE on pancreatic cancer cells’ viability under various conditions. (CREDIT: International Journal of Molecular Sciences)

Identifying the Active Compound

Chemical analysis identified chlorogenic acid methyl ester (CAME) as a key component in FSLE. The fermentation process dramatically increased CAME levels while decreasing chlorogenic acid, suggesting a conversion to a more potent form. CAME was found to be more toxic to cancer cells and to induce programmed cell death more effectively than its precursor.

“Our data demonstrate that CAME exhibits stronger toxicity to cells and pro-apoptotic effects—meaning it encourages programmed cell death—on PANC-1 cells compared to chlorogenic acid alone.”

Narandalai Danshiitsoodol, Associate Professor, Hiroshima University

Further molecular analysis showed CAME interferes with cancer cell cycle progression and significantly boosts genes associated with cell death, such as Bax and Caspase-3, while reducing Bcl-2, a gene that promotes cell survival.

A comparison of the toxic effects of stevia leaf extract (SLE) and fermented stevia leaf extract (FSLE) on pancreatic cancer cells and healthy kidney cells.
The differential toxicity of SLE and FSLE on cancer and healthy cells. (CREDIT: International Journal of Molecular Sciences)

A New Frontier for Natural Therapies

These findings underscore the potential of fermentation to transform common plant extracts into powerful therapeutic agents and highlight the emerging role of probiotics beyond gut health in cancer treatment strategies. Research from other institutions also supports this approach, showing that fermented barley and Panax notoginseng extracts have enhanced efficacy against colon and liver cancers, respectively.

The World Health Organization estimates that pancreatic cancer will be the second leading cause of cancer-related death in many countries by 2030, emphasizing the urgent need for new treatment modalities.

An analysis of the antioxidant properties of stevia leaf extract (SLE) and fermented stevia leaf extract (FSLE).
Assessing the antioxidant activity and protective effects of FSLE against oxidative stress. (CREDIT: International Journal of Molecular Sciences)

Next Steps: From Lab to Living Systems

While these initial laboratory results are highly encouraging, the Hiroshima team is planning the next critical phase: studies in mouse models. This will help evaluate the effectiveness and safety of CAME in a living organism and determine optimal dosages. Success in these preclinical trials could pave the way for human clinical trials, potentially offering a new ray of hope for patients battling pancreatic cancer.

Visual data demonstrating the impact of fermented stevia leaf extract (FSLE) on the proliferation and migration of pancreatic cancer cells.
FSLE’s demonstrated inhibition of cancer cell proliferation and migration. (CREDIT: International Journal of Molecular Sciences)

This research champions a novel approach, leveraging nature’s chemistry, refined by microbial fermentation, to combat one of the most aggressive forms of cancer.

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