Can Cordyceps fight cancer?

‍‍Cordyceps sinensis has been extremely popular in recent years, and the price is expensive, ranging from 300-600/g.
Related products introduce its free amino acids containing protein and amino acids, most of which are essential amino acids for the human body.
It also contains sugar, vitamins, calcium, potassium, chromium, Nickel, manganese, iron, copper, zinc and other elements
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The effect is "regulate immune system function, direct anti-tumor effect"
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However, in May 2018, the former State Food and Drug Administration (CFDA) reiterated that "Cordyceps sinensis is not a health product"
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"Examination of Drug Properties" records its "sweet taste and warm nature, secret essence and nourishing qi, specializing in replenishing life
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"
Since it is a drug, does Cordyceps have an anti-cancer effect? In 1951, German scientist Kaningham isolated cordycepin from Cordyceps militaris
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Scientists have confirmed that the active ingredient of Cordyceps sinensis is cordycepin, which has a chemical property of 3'-deoxyadenosine (3'-dA), which is a natural nucleoside analogue
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Nucleoside analogs are activated by intracellular enzymes and play a role, which is very important for many tumor treatment options
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However, 3'-dA is easily hydrolyzed by adenosine deaminase (ADA) in the blood, leading to insufficient cellular uptake.
In addition, it depends on adenosine kinase (ADK) activation, so only a very small amount of active cordycepin is delivered to the tumor.
Organizations play a role
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Therefore, although the active ingredients of Cordyceps sinensis can exert anti-cancer effects, it is urgent to solve the problem of local tumor drug concentration
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Recently
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The University of Oxford collaborates with the research team of the biopharmaceutical company NuCana to conduct research
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NuCana uses its patented technology ProTide to chemically modify cordycepin extracted from Cordyceps sinensis in the Himalayas to develop a new anti-cancer drug-NUC-7738
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NUC-7738 can produce high levels of active anti-cancer metabolites in cancer cells, and its effectiveness is 40 times that of cordycepin.
The important thing is that it can overcome key drug resistance mechanisms with less toxic and side effects
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This research was published in Clinical Cancer Research with the title "The novel nucleoside analogue ProTide NUC-7738 overcomes cancer resistance mechanisms in vitro and in a first-in-human Phase 1 clinical trial"
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ProTide has been used to produce anticancer nucleoside analogs such as NUC-3373 and NUC-1031
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ProTide mainly combines protective phosphoramide caps with nucleosides to reduce enzymatic hydrolysis and increase the concentration of its active ingredients
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First, the research team used ProTide technology to synthesize pre-activated or monophosphorylated 3'-dA--NUC-7738
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Second, the study compared the anti-tumor effects of NUC-7738 and the parent compound 3'-dA
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By measuring the average half-inhibitory concentration (IC50) of a variety of cancer cell lines, NUC-7738 showed a stronger tumor suppressive effect
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In addition, 3'-dA is dependent on ADA and ADK, but the efficacy of NUC-7738 is mostly not affected by ADA or ADK inhibition
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In order to identify which genes are inactivated resulting in resistance to 3'-dA and NUC-7738, the research team used the nearly haploid human cell line HAP1 to screen for insertional mutations
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The results showed that ADK, HINT1, NUDT2, SMARCA4, UBE2G1 and CREBBP are related to 3'-dA resistance
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Then the research team used 3 different concentrations of NUC-7738 to screen
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Compared with the 3'-dA screen, the ADK gene has no correlation, and surprisingly, the HINT1 gene (involved in purine metabolism) is strongly enriched in all three screens
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Knockout of HINT1 in the HAP-1 cell line and single-cell-derived HINT1 knockout cells has reduced sensitivity to NUC-7738, but has no effect on 3'-dA
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The research team further analyzed the downstream mechanisms of NUC-7738 and 3'-dA.
They mainly affect the expression of mRNA, of which less than 30% are non-coding RNA or pseudogenes
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The genes down-regulated after NUC-7738 and 3'-dA treatment are mainly enriched in cell growth signals (PI3K-AKT-MTOR, NOTCH or wnt-β-catenin signals), cell division (mitotic spindle, G2M checkpoint) and DNA repair (UV-response_U or DNA repair)
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NUC-7738 treatment significantly inhibited the nucleation of NF-kB-p65
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Next, the research team conducted animal experiments, because the half-life of NUC-7738 in the blood of dental caries animals was less than 2 minutes and could not be measured
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The experiment used beagle dogs to determine the maximum non-toxic dose of NUC-7738
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On the basis of successful cell and animal experiments, the research team launched the NuTide: 701 trial, which is the first phase I dose amplification/expansion study to evaluate the safety of NUC-7738 in patients with advanced solid tumors resistant to conventional treatment /Tolerability, pharmacokinetics and pharmacodynamics
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Three centers in Edinburgh, Newcastle and Oxford participated in the Phase 1 clinical trial
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As of June 1, 2021, 28 patients with advanced cancer have been registered
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Patients tolerated NUC-7738 well and showed encouraging anti-cancer activity.
No dose-limiting toxicity was reported
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They also compared the specimens of a melanoma patient before and after treatment
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The results of immunohistochemistry showed that NUC-7738 treatment down-regulated HINT1 and NF-κB
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In addition, RNA sequencing identified 1,069 genes with 2-fold differential expression
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Among them, NF-κB enters the nucleus and NF-κB-dependent TNF-α signaling pathway is significantly down-regulated, and the expression of some cancer-promoting target genes and melanoma-related genes is reduced by 7-40 times
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It is worth noting that the results on leukemia-derived HAP1 cells, acute monocytic leukemia-derived THP1 cells, and human clear cell renal cancer in vitro model results are similar to those found in patient-derived melanoma specimens, indicating that NF The influence of -κB signaling pathway may be a common feature of NUC-7738 treatment
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This study shows that NUC-7738 can overcome the key cancer drug resistance mechanism and produce higher anti-cancer activity than cordycepin
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Phase 1 clinical trials showed good anti-cancer activity and tolerance, supporting NUC-7738 as a new cancer treatment drug for further clinical evaluation
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However, be aware that the side effects caused by taking Cordyceps include skin rash, itching, constipation, abdominal distension, reduced bowel movements, and menstrual disorders.
Long-term use may be harmful to the kidneys; therefore, rational use is the kingly way
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Reference: Clin Cancer Res.
2021 Sep 8;clincanres.
1652.
2021.
doi: 10.
1158/1078-0432.
CCR-21-1652.
Online ahead of print.
The novel nucleoside analogue ProTide NUC-7738 overcomes cancer resistance mechanisms in vitro and in a first-in-human Phase 1 clinical trialps: This article only truthfully introduces the latest scientific research progress, and does not constitute purchase or use advice
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Author|Ann Editor|Little Ears‍‍