New research uncovers promising role of vitamin B6 in targeting pancreatic cancer

27 Feb 2024 --- Researchers suggest a pathway for potential new therapeutic strategies against pancreatic cancer based on vitamin B6. This vitamin supports immune cells, or natural killer cells, to counter various diseases. However, in someone with pancreatic cancer, cancer cells use up all the vitamin B6 that immune cells need to fight it, blocking their function.

Instead of simply giving additional vitamin B6 — which only helps pancreatic cancer cells grow more — the research team reveals a three-part strategy, which successfully reduced the amount of pancreatic cancer cells in mice.

The team first blocked the pathway through which cancer cells take up the vitamin by reducing the expression of a specific gene. Next, the team supplied more vitamin B6 and then utilized a therapy to enhance the function of natural killer cells.

“Pancreatic cancer is very difficult to treat, and only 11% of people who are diagnosed survive for five years,” says lead researcher Kamiya Mehla, Ph.D., an associated professor of oncology at the University of Oklahoma College of Medicine, US.

“It’s important that researchers study pancreatic cancer from many different angles to develop new treatments. My laboratory is focused on the role of vitamin B6 because we know it boosts the immune system, but we need to understand more about how it affects cancer cells. We hope our work opens new avenues for developing novel treatments for pancreatic cancer.”

Natural sources of vitamin B6 include meat, such as chicken, fish and bananas.

Vitamin B6 depletion
Mehla’s team discovered the new strategy after studying how cancer cells deplete vitamin B6 and then devised steps to impede them. The findings are published in Cancer Discovery.

Pancreatic cancer cells actively consume the vitamin to support one-carbon metabolism, improving tumor cell growth and causing vitamin B6 deprivation in the tumor microenvironment. In contrast, a lack of the vitamin limits the proliferation of these cells in vitro.

At the same time, natural killer cells require the vitamin to break down intracellular glycogen, a critical energy source for their activation. According to the study, glycogen metabolism regulates the immune response in innate and adaptive immune cells.

The team found that supplementing the vitamin with the one-carbon metabolism blockage diminishes tumor burden by amplifying the antitumor immunity of natural killer cells.

“That was encouraging to discover,” Mehla comments, “it is important to know because the immune system needs to be strong for other treatments, like chemotherapy, to be effective. Therapy will not work if the immune system cannot do its part.”

Animal foods, fish, peanuts, soya beans, oats and bananas are all dietary sources of vitamin B6.Earlier this year, the American Cancer Society called for a dietary shift to prevent cancer, warning that red and processed meat consumption can increase the risk of colorectal, pancreatic and prostate cancer.

Meanwhile, the WHO International Agency for Research on Cancer predicts an increase of 77% from 2022 to 2050 in new cancer cases globally, driven by tobacco and alcohol use, obesity and air pollution.

Research gaps
The researchers caution that, despite the promising results, the molecular and cellular circuitries underlying the observations still need to be clarified.

It is unclear if a pancreatic tumor systemically affects the absorption of vitamin B6 in the entire body. For example, while animal foods are the richest sources of the vitamin, the researchers highlight that digestive difficulty is one of the most common symptoms associated with pancreatic cancer as enzymes in the organ are responsible for digestion, especially of animal foods.

The study also notes more research is needed to address the function of vitamin B6 in the early stage of cancer development. Its data indicates that the vitamin stimulates pancreatic cancer growth. At the same time, earlier studies note that higher circulating levels of the vitamin in the blood are linked to a reduced incidence of pancreatic cancer.

For example, earlier research indicates that limiting vitamin B6 impairs T-cell responses in mice and humans — a white blood cell part of the immune system that also targets cancer cells.

Mehla calls for more research to determine how to stimulate the immune system against tumors.Next steps
Over the past year, Mehla has received US$2.6 million in grants from the National Institutes of Health and the US Department of Defense to continue her research on employing the body’s immune system against invaders like pancreatic cancer.

She plans to continue the research and expand into related concerns. As pancreatic cancer impacts other organs in its goal to gain more nutrients, Mehla will examine how limiting vitamin B6 affects other organs, such as the liver, when cancer cells are present.

In addition, she is studying whether a lack of vitamin B6 contributes to cachexia — a muscle-wasting condition affecting the majority of patients with pancreatic cancer. The US Department of Defense funds this research as military members face an increased risk of developing pancreatic cancer because they are exposed to hazards such as radiation and chemical toxins.

“When patients have such a dramatic muscle loss, they are less likely to respond to treatment,” explains Mehla. “Pancreatic cancer is a systemic disease. It’s not just sitting there. It’s trying to extract nutrients from multiple areas to help it survive. That’s why it’s important to look broadly at how we can stimulate the immune system against tumors.”

By Jolanda van Hal

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