Antioxidants are really a big star.
It can be seen in various health, health care and skin care and beauty products, and it has also been reported to have the ability to fight cancer.
However, things are counterproductive. At the beginning of this year, we reported that antioxidant vitamin E can’t be eaten indiscriminately. If there is no corresponding gene mutation, the risk of cancer will not decrease but increase.
Recently, a Swedish team found that once again the antioxidantAgent: Vitamin E and N-acetylcysteine (NAC) are a big hit. They confirmed that these antioxidants can promote lung cancer metastasis, related research was published in the top academic journal "Cell" . The corresponding author of the paper is Martin O. Bergo, and the first author is Clotilde Wiel.
And another American team independently made a similar result. The paper was also published on Cell. The corresponding author is Michele Pagano, and the first author is Luca Lignitto.
These two studies support each other, confirm each other, and fire a fierce fire on the antioxidants of dietary supplements!
Left: Michele Pagano (Howard Hughes Medical Institute)
Right: Martin O. Dr. Bergo (Kaolinska Institute of Medicine)
The reason why antioxidants are so hot these years is that people have fear of reactive oxygen species in the human body.
These reactive oxygen species are indeed hateful , They have strong oxidizing ability and can destroy fatty acids, proteins, DNA and other substances in cells. Of course, we don’t need to worry too much in general, because cells can use oxygenCatalytic enzymes, reducing substances (such as vitamin E), etc., remove these reactive oxygen species.
But when there are too many reactive oxygen species, the situation is not so good, which can cause cell senescence and death.
How much is the lethality of reactive oxygen species on cells? In fact, the commonly used antiseptics in our lives, 84 disinfectant, chlorine, potassium permanganate, and ozone in the washing cabinet, all eventually kill bacteria by generating active oxygen.
In the human body, the increase of reactive oxygen species is related to the occurrence of many diseases, such as arteriosclerosis, hypertension, and cataracts.
Moreover, in the past few decades, people also believed that reactive oxygen species would promote the occurrence and development of cancer.
The role of reactive oxygen species (vitotox.com)
So, at first glance, supplementing antioxidants (reducing substances) to offset the hateful active oxygen seems reasonable.
However, since active oxygen is a sharp sword that can sterilize and kill its own cells, it can also kill cancer cells. In fact, active oxygen is the human body’s ability to execute its own betrayal.Zi-the weapon of cancer cells.
Scientists have found that reactive oxygen species can limit the development of cancer, and supplementing antioxidants will help cancer remove this obstacle .
Moreover, they also confirmed in mice that vitamin E and NAC can promote the progression of primary lung cancer . Of course, the premise is that the Kras2 gene has a mutation.
Picture from drweil.com
For cancer, the most terrifying thing is metastasis.
Antioxidants will promote Cancer progression, does it also affect cancer metastasis? No one has studied it yet.
This is an urgent issue that needs to be clarified.
Researchers from Martin’s team, in Kras2 They were tested in a mouse model of lung adenocarcinoma with a single cell and Kras2 p53 double cell.
They fed the lung adenocarcinoma mice with antioxidants (vitamin E or NAC) for a week, and found that In these antioxidant-eating tumor mice, the incidence of lymph node metastasis is 6-7 times that of the control mice! Not only that,Antioxidants can also promote the distant metastasis of lung adenocarcinoma.
Researchers separated the cancer cells from mice in the antioxidant group and the control group, and expanded them in vitro. It was found that the cancer cells in mice that had eaten antioxidants had stronger Invasiveness and transfer ability.
When they were injected intravenously into mice, it was found that the anti-oxidant group had a much stronger ability to metastasize cancer cells remotely than the control group. A large number of metastases have formed in the kidneys, heart, and chest cavity, and have entered the lymph nodes.
mTC is the control group, and mTN is the antioxidant group
In other words, antioxidants Oxidants make cancer cells more terrifying.
Why do the cancer cells of mice that eat antioxidants become so terrible?
Researchers hurry up They were tested.
The first thing to be tested is of course the level of reactive oxygen species. Not surprisingly, the level of reactive oxygen species in these cancer cells is lower, so it seems that it is indeed the "credit" of antioxidants. .
Later, through a series of experiments, they revealed the mechanism by which antioxidants promote the metastasis of cancer cells.
It turns out that antioxidants can remove reactive oxygen species in cells, and reduceThe level of free hemoglobin in the cell, this will prevent a protein called BACH1 from being degraded and increase its accumulation. The BACH1 protein can enhance the glycolytic pathway[4,5 ].
The author mentioned that after the BACH1 protein enhances the glycolytic pathway, it increases the secretion of lactic acid, induces the apoptosis of surrounding healthy cells, and promotes the degradation of the extracellular matrix, Favorable conditions for cancer cell metastasis; while the by-products in the glycolysis pathway, such as pyruvaldehyde, will enhance epithelial-mesenchymal transition. In addition, glycolysis produces more ATP, strong>It also provides energy for the cytoskeleton and enhances the motility of cancer cells.
The molecular mechanism of antioxidants to promote metastasis
These will promote the metastasis of cancer cells.
In addition, BACH1 protein has long been found to be highly expressed in patients with lung adenocarcinoma, and is associated with a worse prognosis.
All this shows that antioxidants It can increase the accumulation of BACH1 protein to promote cancer metastasis.
Another study published in Cell at the same time also confirmed that BACH1 protein promotes the metastasis of lung adenocarcinoma cells. And, They also found that Keap1 or Nfe2l2 mutations that occur 30% in human lung cancer will also Enhance the level of BACH1, and then promote lung cancer metastasis through its downstream signaling pathway.
Therefore, these two studies actually converge on the BACH1 protein, both reveal an important mechanism of lung cancer metastasis.
The mechanism they discovered will provide a new target for the treatment of lung cancer.
The editor talks about it
It’s too late.......
 Clotilde Wiel et al. BACH1 Stabilization by Antioxidants Stimulates Lung Cancer Metastasis. Cell, 2019, 178, 1–16. https://doi.org/10.1016 /j.cell.2019.06.005
 Luca Lignitto et al. Nrf2 Activation Promotes Lung Cancer Metastasis by Inhibiting the Degradation of Bach1. Cell, 2019, 178, 1–14. https://doi.org/10.1016/j.cell.2019.06.003
 KLG, Ibrahim MX, Wiel C, et al. Antioxidants can increase melanoma metastasis in mice[J]. Science Translational Medicine, 2015, 7(308).
 Gozzelino R, Jeney V, Soares MP, et al. Mechanisms of cell protection by heme Oxygenase-1[J]. Annual Review of Pharmacology and Toxicology, 2010, 50(1): 323-354.
 Zenkekawasaki Y, Dohi Y, Katoh Y, et al. Heme Induces Ubiquitination and Degradation of the Transcription Factor Bach1[J]. Molecular and Cellular Biology, 20a07, 27(19): 6962-6971.
Author of this article | Low Temperature Artist