Stevia may soon offer more than just sweetness. In the lab, researchers found that when fermented with a bacterium from banana leaves, this natural plant extract targets pancreatic cancer cells – while leaving healthy kidney cells unharmed.
“Globally, the incidence and mortality rates of pancreatic cancer continue to rise, with a five-year survival rate of less than 10%,” said study co-author Narandalai Danshiitsoodol from Hiroshima University.
“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.”
Fermented stevia for cancer therapy
The researchers used Lactobacillus plantarum SN13T, a bacterium from banana leaves. They fermented stevia leaves and compared the result to a regular extract. The fermented version (FSLE) worked better in every way.
“To enhance the pharmacological efficacy of natural plant extracts, microbial biotransformation has emerged as an effective strategy,” said Masanori Sugiyama.
“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 researchers didn’t just mix things and hope. They optimized fermentation time, temperature, and oxygen levels. Stevia turned out to be most potent when fermented for 72 hours, without oxygen, at 37°C.
Fermented stevia hits cancer cells hard
Fermented stevia killed pancreatic cancer (PANC-1) cells more efficiently than the non-fermented extract. At the same time, it barely touched healthy HEK-293 cells, even at high doses. That balance is rare and valuable.
At some concentrations, FSLE didn’t kill cancer cells immediately. Instead, it slowed their growth. The cancer cells looked weak, lost shape, and stopped sticking together. Under the microscope, they looked scattered and unhealthy.
Healthy kidney cells stayed mostly unaffected. This points to selectivity – a key feature for safe treatments.
Strong antioxidant effects
Cancer isn’t just about rogue cells. Oxidative stress plays a big role. Fermented stevia turned out to be a powerful antioxidant too.
In lab tests, it neutralized free radicals more effectively than non-fermented extract. It hit 94% scavenging power in the DPPH assay and 75% in ABTS. Even when healthy cells were exposed to hydrogen peroxide, FSLE helped them survive.
Fermentation likely created new compounds. The researchers suspect chlorogenic acid transformed into chlorogenic acid methyl ester (CAME), a more active form. Fermented stevia contained lots of it. The raw extract had none.
Powerful compound fights cancer cells
CAME packed more punch than chlorogenic acid. It stopped cancer cell growth and triggered their self-destruction.
Its IC50 – the dose that kills half the cancer cells – was just 119.1 µg/mL. For regular chlorogenic acid, it was 189.6 µg/mL. That’s a big difference. CAME shut down cancer cells by blocking their cell cycle and making them commit apoptosis.
Flow cytometry showed CAME, produced by fermented stevia, locked the cells in the G0/G1 phase. That’s the stage before a cell starts duplicating. It also caused the cells to release cytochrome c and activate caspases, which break down dying cells from the inside.
Altered gene activity
At the gene level, things got interesting. CAME dialed up pro-apoptotic genes like Bax, Bad, Caspase-3, Caspase-9, and Cytochrome c.
The compound also boosted E-cadherin, a gene linked to reduced cancer migration. Meanwhile, it shut down Bcl-2, a gene that normally stops cells from dying.
This gene activity supports what the microscope and assays showed. The cells didn’t just die randomly. CAME pushed them into a specific self-destruct mode, the mitochondrial pathway.
Stevia: More than just a sweetener
Fermentation changed the story. It gave stevia extract a new weapon – a compound that targets cancer while keeping healthy cells safe. That transformation seems to happen through specific enzymes from the SN13T strain.
“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.”
Upcoming cancer research with stevia
The team plans to move beyond the lab dish. Mouse studies come next. That will show whether fermented stevia works in living systems with real immune responses and complex metabolism.
“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,” said Danshiitsoodol.
This research suggests that with the right microbes, even a simple leaf can evolve into a targeted therapy. Not bad for a sugar substitute.
The study is published in the International Journal of Molecular Sciences.
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