Recently, a news report submitted by a Chinese website Sina technology and this article is completely based on their research and findings, we didn’t add anything from our side… According to them, the “vitamin C can be used as a potential small molecule for the treatment of kidney cancer “.
This is to start with the innate superior conditions of Vitamin C (Vc). Vc is an essential nutrient element in our daily life. Fresh dates, kiwi, grapefruit, green pepper, tomato, strawberry, cucumber, citrus, etc. are all rich in Vc. It can enhance the body’s immune function, anti-oxidation, and also has a cosmetic effect.
In 1970, Nobel Prize winner and biochemist Pauling issued a document saying that Vc can be used to fight cancer. After that, many people stood up and suspected that Vc’s talents were different. It was once at the forefront of the turmoil and controversy continued. However, research on the relationship between Vc and tumor has never stopped.
According to the existing research, the main reason why Vc can inhibit tumor cells is to produce reactive oxygen species (ROS) by the redox reaction, which can kill cancer cells. In clinical trials, high dose intravenous injection can be performed on patients. To achieve this, it is difficult to achieve the same blood concentration by the simple oral administration. This is the reason why Pauling was able to propose Vc anti-tumor and the subsequent studies could not be reproduced.
The existing Vc anti-tumor research is based on the direct killing of cancer cells, which is essentially indistinguishable from radiotherapy and chemotherapy and subsequent tumor-targeted therapy.
Low doses of vitamin C can fight kidney cancer!
We know that cancer patients lack vitamin C. Therefore, scientists treated the renal cancer cell line with Vc and Vc derivative magnesium phosphate (the derivative is more stable) at physiological concentration (the plasma concentration of healthy human Vc is about 100 μM), and found that a DNA in the cell is demethylated. The activity of the Tets enzyme is increased, so that the modification of DNA, 5-hydroxymethylcytosine (5hmC), is elevated, and the treatment under such low dose conditions inhibits the growth and migration of tumor cells to some extent.
In the end, did Vc use the trick to successfully fight kidney cancer? In the transparent renal cell carcinoma, 5hmC in tumor cells is generally down-regulated relative to normal cells, which is closely related to the poor prognosis of patients. Tets can oxidize 5mC to produce 5hmC, while low-dose Vc can be processed for a long time. By increasing the activity of Tets enzyme, the DNA can be re-applied with more 5hmC modification, and it can be reprogrammed to reduce the degree of tumor malignancy. At the same time, this low-dose treatment has little toxic side effects on the cells.
So, does this method work in vivo? In subsequent animal experiments, the scientists found that the same results were obtained in nude mice xenografts (tumor transplanted on immunodeficient mice) and primary cultured cells of primary renal cell carcinoma: 5hmC level rise High, the malignant degree of tumor cells is weakened.
Anti-cancer tips for vitamin C: Apparent and transcriptional reprogramming
Of course, in addition to the experimentally impressive and pleasing results, the scientists also integrated the analysis of the sequencing data. Methylated DNA Immunoprecipitation Sequencing (hMeDIP-seq) was used to detect DNA 5hmC levels; H3K27ac Chromatin Immunoprecipitation (ChIP-seq) was used to identify genes that significantly increase gene expression “Super enhancer”. Super-enhancers are a series of sequences that play a regulatory role in DNA. With it, the corresponding genes will be abnormally activated and efficiently transcribed. By analyzing the hMeDIP-seq data of Vc and its derivatives on renal cancer cell lines at physiological concentrations, scientists can clearly see the apparent reprogramming pattern of DNA 5hmC, which is more similar to healthy cells.
So, where is this 5hmC appearing to alleviate the symptoms of kidney cancer? Further verification by ChIP-seq sequencing revealed that in the long-treated renal cancer cells of Vc and its derivatives, the 5hmC up-regulation region mainly appeared in the enhancer region, especially the renal tissue-associated super enhancer. These super-enhancer-regulated genes are mainly concentrated in the HIF signaling pathway, which is closely related to the occurrence of renal clear cell carcinoma. That is to say, Vc may regulate the renal tissue-associated super-enhancer to play a role in anti-cancer through changes in 5hmC modification. Changes in DNA 5hmC modification ultimately also cause changes in gene expression.
From the results of these data analysis, we can find that Vc and its derivatives can induce 5hmC reprogramming in renal cancer cells and change the differentiation status of renal cancer cells. Overall, Vc returns the kidney cancer cells to their original state, preventing them from being bohemian and plagued.
This highly meaningful study was first demonstrated in renal cancer cells. Vc can increase the level of 5hmC by promoting the activity of the Tets enzyme, reprogramming the DNA to a “normal” state, thus reversing the malignant phenotype of renal cancer cells and exerting resistance. Tumor effect. This discovery not only provides new ideas and potential new strategies for the treatment of renal cancer but also provides the latest basis for the important role of epigenetics in cancer therapy.
The results were completed by the Ci Weimin Research Group of the Beijing Institute of Genomics of the Chinese Academy of Sciences and the Zhou Liqun Research Group of the First Hospital of Peking University. The issue of “Restoration of 5-hydroxymethylcytosine by ascorbate reduces kidney tumor growth” was published online in EMBO Reports. At present, the research has been patented, and the prospective study of Vc combined with targeted drugs for the treatment of transparent renal cell carcinoma has been carried out in cooperation with the unit. In the future clinical treatment, Vc and its derivatives can be used alone or in combination to treat transparent kidney. Cellular cancer shows a promising future.