Study shows common artificial sweetener has huge potential to kill cancer

Pancreatic cancer hides in plain sight. Symptoms often show up late, and the disease shrugs off many standard treatments. That’s why the five-year outlook is grim and the need for smarter ideas is urgent.

“Globally, the incidence and mortality rates of pancreatic cancer continue to rise, with a five-year survival rate of less than 10%,” lamented Narandalai Danshiitsoodol from Hiroshima University, who is co-author of a recent study focusing on this issue.

One idea now getting the attention it deserves takes a cue from everyday plants and friendly microbes.

Instead of designing a new drug from scratch, researchers asked a simple question with big consequences: can we reshape natural plant compounds, like Stevia, so they put pressure on pancreatic cancer cells while going easier on healthy cells?

Repurposing Stevia as a cancer drug

Stevia, known for its natural sweetness, is packed with bioactive molecules beyond its sugar-free charm. Those molecules don’t all act the same in the body. Some do a little. Some do a lot.

The twist in this study was to run a stevia leaf extract through a controlled fermentation step and see whether that increased its effect against pancreatic cancer cells.

“Pancreatic cancer is highly invasive and prone to metastasis, showing significant resistance to existing treatments, such as surgery, radiotherapy and chemotherapy,” Narandalai Danshiitsoodol explained.

“As such, there is an urgent need to identify new and effective anticancer compounds, particularly those derived from medicinal plants.”

The team made two mixtures for head-to-head testing: a standard stevia leaf extract (SLE) and a fermented version (FSLE) prepared with a Lactobacillus plantarum strain.

Then they put both through antioxidant screens and a series of cell tests that looked at survival, growth, movement, and adhesion – the traits that help tumors spread.

Fermenting Stevia to fight cancer

Antioxidant capacity jumped after fermentation. DPPH and ABTS are lab tests that measure how well something soaks up “free radicals,” which are reactive molecules that can damage cells.

In those tests, the fermented extract (FSLE) did a better job cleaning up those radicals than the unfermented extract. Think of it like two sponges in a spill – the fermented one absorbed more.

In a cell-stress setup that floods cells with hydrogen peroxide, the fermented mix also provided stronger protection. Oxidative stress is tied to cancer growth and spread, so this shift matters.

But the bigger test is whether those changes affect cancer cells. When the team exposed a pancreatic cancer cell line (PANC-1) to FSLE, cell viability dropped more than it did with the regular extract at matched doses.

“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,” said corresponding author Masanori Sugiyama, professor in the Department of Probiotic Science for Preventive Medicine.

Sugiyama’s lab has isolated and evaluated the health benefits of more than 1,300 lactic acid bacteria (LAB) strains from fruits, vegetables, flowers, and medicinal plants.

Selectivity matters

Hitting tumors is one thing. Sparing healthy tissue is another. At the same doses, FSLE showed minimal harm to a noncancerous human cell line (HEK293).

That kind of selectivity is a key box to check before any lab result earns real interest.

In separate functional tests, FSLE made it harder for PANC-1 cells to form new colonies, migrate into a scratch gap, and adhere in ways that support spread.

Those shifts point in the same direction: less growth, less movement, less anchoring.

Active ingredient

Fermentation doesn’t just boost or shrink effects; it can change the chemical mix.

The researchers first sorted the chemicals in the fermented stevia using HPLC, a tool that separates mixtures into their parts.

They then identified those parts with two “fingerprinting” methods – NMR and mass spectrometry – and focused on one molecule called chlorogenic acid methyl ester (CAME).

When they tested CAME by itself on a lab-grown pancreatic cancer cell line (PANC-1), it showed strong anticancer activity, and they also confirmed that the fermented stevia extract contained a meaningful amount of CAME.

How CAME works with Stevia to fight cancer

CAME worked against the cancer cells in two big ways. First, it stopped a lot of them from getting ready to divide, like hitting the “pause” button before they could copy their DNA and make more cells.

Second, it pushed some of the cells to go through apoptosis, which is just the body’s natural way of cleaning up damaged or dangerous cells – kind of like programmed self-destruction.

The genes inside the cells backed this up. “Death-promoting” signals (like Bax, Bad, and caspase proteins) went up, while “survival” signals (like Bcl-2) went down.

Another helpful change was that E-cadherin, a protein that helps cells stick together, went up too. That makes it harder for cancer cells to break off and spread around the body.

So overall: CAME slows the cancer cells, encourages them to self-destruct, and makes them less able to spread.

“This microbial transformation was likely due to specific enzymes in the bacteria strain used,” Danshiitsoodol explained.

“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.”

Cancer, Stevia, and next steps

There’s a clear to-do list. Researchers need animal studies to see whether FSLE or purified CAME reaches tumors at useful levels, how the body handles them, and whether side effects appear.

They also need to test other pancreatic cancer models, refine Stevia delivery, and dial in dosing. If that groundwork looks solid, the next rung would be early-stage trials in people.

To sum it all up, pancreatic cancer needs more treatment options. Studies like this bring a modest, methodical mindset: start with something familiar, change it in a defined way, measure it across the key cancer behaviors, and identify what’s doing the heavy lifting.

It’s not flashy. It’s stepwise. That’s how many useful therapies begin.

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 full study was published in the International Journal of Molecular Sciences.

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