June 29, 2022

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Science: Warburg effect brings new methods of cancer treatment

Science: Warburg effect brings new methods of cancer treatment



 

Science: Warburg effect brings new methods of cancer treatment. Science: When the Warburg effect was born 100 years ago, Li Ming’s team solved the puzzle and brought a new method of cancer treatment.

 

In the cell, there are two ways of sugar metabolism: mitochondrial oxidative phosphorylation and glycolysis. In normal mammalian cells, glycolysis is inhibited under aerobic conditions.

 

However, in 1921, the German scientist Otto Warburg observed a strange phenomenon: the glycolysis of cancer cells is extremely active, even under conditions of sufficient oxygen, the glycolysis of cancer cells is as active.

This type of glycolysis of cancer cells in an aerobic state is also known as the “Warburg effect.” Otto Warburg also won the Nobel Prize in Physiology or Medicine in 1931 for discovering cellular respiration oxidative transferase.

 

Glycolysis is a process in which glucose or glycogen in cells is decomposed into lactic acid under anaerobic or hypoxic conditions while producing a small amount of ATP. This type of glucose metabolism that does not require oxygen is fast, but will cause a lot of energy in glucose to be wasted, so why do cancer cells adopt this inefficient glycolysis method?

 

Since the discovery of the “Warburg effect”, many scientists have put forward various conjectures to try to explain this peculiar phenomenon. For example, some people think that the mitochondria of cancer cells are defective, causing cancer cells to be unable to oxidize and decompose glucose, but none of these conjectures can withstand time. test.

 

On January 21, 2021, Ming Li’s team at the Memorial Sloan Katherine Cancer Center in the United States published a research paper entitled: Glycolysis fuels phosphoinositide 3-kinase signaling to bolster T cell immunity in Science.

 

This research provides a new answer to the “Warburg effect”. The study showed that there is a previously undiscovered link between Warburg’s metabolism and the activity of PI3 kinase (PI3K), which is achieved through lactate dehydrogenase A (LDHA).

 

Cancer cells can use Warburg metabolism to maintain the activity of the PI3K signaling pathway, thereby ensuring the continued growth and division of cancer cells. This discovery challenges long-standing views in textbooks. More importantly, this study proposes a promising cancer treatment that can inhibit the Warburg “switch” of lactate dehydrogenase A (LDHA). Cancer cells grow and are used to treat cancer.

 

Science: Warburg effect brings new methods of cancer treatment

 

 

Challenging textbook views

Li Ming’s team studied Warburg metabolism in immune cells. In fact, immune cells sometimes rely on this seemingly inefficient way of metabolism.

When the immune system detects an infection, the activated effector T cells (Teff) will change from the typical aerobic metabolism to Warburg metabolism as the number increases and the anti-infection mechanism strengthens. The key switch that controls this transition is lactate dehydrogenase A (LDHA), which is produced in response to PI3K signal transduction.

 

The result of this conversion is that after glucose is only partially decomposed, ATP is rapidly produced in the cytoplasm for energy, without waiting for further decomposition in the mitochondria.

 

Li Ming’s team found that in mice, T cells lacking lactate dehydrogenase A (LDHA) cannot maintain their PI3 kinase (PI3K) activity and therefore cannot effectively fight infection. This implies that lactate dehydrogenase A (LDHA), a metabolic enzyme, is controlling the signaling pathway that requires PI3K.

 

For a long time, people believed that metabolism is a secondary factor in growth factor signal transduction, that is, growth factor signal transduction drives metabolism, and metabolism supports cell growth and proliferation.

 

The study found that metabolic enzymes like lactate dehydrogenase A (LDHA) can affect growth factor signal transduction through PI3K. This discovery challenges the long-standing views in textbooks.

 

 

Why T cells take Warburg metabolism

Like other kinases, PI3 kinase (PI3K) relies on the consumption of ATP to perform its functions. Since ATP is the net product of Warburg metabolism, a positive feedback loop is established between Warburg metabolism and PI3K activity to ensure the continuous activity of PI3K. Cell division.

 

As for why activated effector T cells (Teff) preferentially adopt Warburg metabolism, Professor Li Ming believes that this is because immune cells need to divide rapidly and increase anti-infection mechanisms, so they need to quickly generate ATP for energy, this positive feedback loop It can be ensured that once it starts, it will continue until the infection is eradicated.

 

 

Link to cancer

Although these conclusions were found in immune cells, the researchers said that this is clearly similar to cancer. In the context of cancer, PI3K is also a very critical kinase in cancer cells. It is the PI3K signaling pathway that sends out the growth signal of cancer cell division, and the PI3K signaling pathway is one of the most active signaling pathways in cancer.

 

Like immune cells, cancer cells can use Warburg metabolism to maintain the activity of the PI3K signaling pathway, thereby ensuring the continued growth and division of cancer cells.

 

This research provides a new answer to the “Warburg effect”. The reason why cancer cells choose inefficient glycolysis is because this metabolic method can maintain the activity of the PI3K signaling pathway, thereby ensuring the continued growth and division of cancer cells.

 

More importantly, these findings suggest a promising cancer treatment method. By inhibiting the Warburg “switch” of lactate dehydrogenase A (LDHA), it can inhibit the growth of cancer cells and then be used to treat cancer.

 

It is worth mentioning that on October 21, 2020, Professor Li Ming’s team published two papers “back-to-back” in the journal Nature, one basic research and one translational research, and proposed the “environmental cancer immunotherapy”. It is expected to be an important supplement to existing cancer therapies. Click for details: Li Ming’s team invented “Cancer Environmental Immunotherapy”

 

 

 

 

(source:internet, reference only)


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