August 11, 2022

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Is it possible to starve cancer cells by not eating sugar?

Is it possible to starve cancer cells by not eating sugar?

Is it possible to starve cancer cells by not eating sugar?  Enlightenment from NATURE’s new research…

Humans have been fighting cancer for one or two hundred years. However, we have not yet been able to conquer most cancers.

Immune escape, metabolic synthesis, apoptosis… The medical community and scientists are trying to discover patterns from the various mechanisms of tumor cells and find ways to inhibit tumors.

German physiologist Otto Warburg put forward the “Warburg effect” which was a sensation. The theory of “starve cancer cells” has been sought after.

What exactly is the Warburg effect? Could it really be possible to “starve cancer cells” through this approach?

Hey, let me tell you about it.

In 1924, Otto Warburg proposed: Compared with normal mature cells, tumor cells absorb more glucose with higher efficiency to produce energy and meet the needs of rapid growth.

Is it possible to starve cancer cells by not eating sugar?

Picture: Otto Warburg

Even in the case of adequate oxygen supply, tumor cells mainly take up a large amount of glucose and produce a large amount of lactic acid through the glycolytic pathway.

In layman’s terms, tumors prefer to consume a lot of glucose through anaerobic respiration.

This theory also helped us discover a good way to observe the traces of tumor cells-PET-CT.

PET-CT uses a tracer to observe cell metabolism, function, blood flow, cell proliferation and receptor distribution in the body and lesion tissue. Generally speaking, it looks like this after the photo-

Is it possible to starve cancer cells by not eating sugar?

It can be clearly seen that the bright spots in the picture are different from other body tissues

The results of PET-CT are intuitive and can detect most types of primary and metastatic epithelial tumors, and the sensitivity and specificity are as high as 90%.

However, sometimes, doctors will find that the concentration of glucose (FGD) observed in PET-CT imaging has undergone pathological examination and found that there are no tumor cells.

A recent study found that although tumor cells love sugar, they are not the boss of the “sugar-eating world”. Myeloid immune cells love sugar more!

Is it possible to starve cancer cells by not eating sugar?

Research screenshot

This research was published in “Nature” [1]. The researchers found that in tumor tissues (including a large number of tumor cells and infiltrating immune cells, mesenchymal cells, etc.), all cancer cells consume about two-thirds of the total glucose, while myeloid immune cells consume about two-thirds of the total glucose. It accounts for one-third of glucose intake.

Is it possible to starve cancer cells by not eating sugar?

Figure: CD45- (tumor cell population) uptakes FDG the most

The researchers then divided the cells in mouse subcutaneous MC38 tumors into CD45- (tumor cells) and CD45 + (immune cells) populations, and measured the 18F radioactivity of the two cells. The results are very interesting: as far as individual cells are concerned, the uptake of FDG by CD45+ in the tumor is greater than that of CD45-.

In other tumor models: human renal cell carcinoma (RCC), mouse colon cancer (MC38), mouse colon cancer (CT26), mouse renal cell carcinoma (Renca), mouse colon cancer (AOM/DSS induced), and (PyMT) Gene Breast Cancer (GEMM) all showed the same results.

Figure: The results in multiple tumor models are basically the same

It shows that in the tumor microenvironment with sufficient glucose, the immune cells infiltrated in the tumor take in more “sugar” than the tumor cells.

It seems that “no sugar” is not that simple. Be careful to hurt the enemy a thousand, and one thousand two! ! !

But this study has another discovery-tumor cells prefer to take glutamine!

Glutamine sounds familiar, but what is it?

Glutamine (Gln) is the most abundant non-essential amino acid in the human body. It is involved in the synthesis of glutathione in the cell and maintains the intracellular redox homeostasis [2].

Studies have found that among all the amino acids consumed by tumor cells, Gln has the largest demand. The consumption rate of Gln in tumor cells is 5-10 times that of normal cells [2].

In the Nature study, the results of PET-CT imaging analysis showed that MC38 tumor cells showed a higher 18F-Gln uptake rate. Compared with CD45+ immune cells in MC38 tumors, CD45-cancer cells have a higher rate of uptake of 18F-Gln. And, after inhibiting glutamine transport, tumor cells increased their glucose uptake.

Figure: CD45-cancer cells have a higher affinity for 18F-Gln

This shows that in the presence of glutamine, tumor cells prefer glutamine as a raw material for biosynthesis and energy.

Recent studies have shown that inhibition of Gln metabolism and transport can effectively inhibit tumor cell growth and induce tumor cell apoptosis or autophagy.

In addition, glutamine is also closely related to the chemotherapy resistance of tumors. Researchers at the Cancer Center of the Keck School of Medicine of the University of Southern California found that after chemotherapy in obese patients with acute lymphoblastic leukemia, the expression of glutamine synthase in adipocytes in the bone marrow increased, and the glutamine content in the microenvironment increased significantly, which can help leukemia Cells resist the therapeutic effects of L-asparaginase [3].

Research screenshot

Researchers from Case Western Reserve University in the United States[4] found that in the experiment, rectal cancer cells were injected into the flanks of athymic nude mice. After the tumors grew, the mice were divided into four groups. Except the blank control group, the others The three groups were given glutaminase inhibitor (CB-839), 5-fluorouracil (5-FU) and CB-839 and 5-FU at the same time, and the tumor size was measured weekly thereafter.

Figure: Compared with other groups, the tumor volume in the CB-839+5FU group was significantly reduced

It was found that the use of CB-839 inhibited the growth of xenotransplanted colon cancer tumor cells with PIK3 gene mutations. What is even more exciting is that 1/3 of the tumor mice were completely cured after receiving the CB-839+5FU combination treatment.

Sum up: 

Although these mouse experiments cannot be applied to the clinic as soon as possible, the metabolic pathway of glutamine may really become an important target for “starved cancer cells.”

By the way, although “starving cancer cells” is feasible theoretically and clinically.

However, it is not recommended to go on a hunger strike or avoid sugar and protein in order to “starve cancer cells”… After all, the body is the capital of the revolution.

(source:internet, reference only)

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