MAHEK KHATRI AND DHANUSHA NADAR CANCER DRUG FROM HIMALAYAN FUNGUS CORDYCEPIN AS AN ANTICANCER DRUG
- TCSC Botany
- Jul 8, 2022
- 3 min read
In recent research carried out by University of Oxford scientists in collaboration with biopharmaceutical company Nucana, a new molecule Cordycepin was extracted from a Himalayan fungus. This phytochemical is being said to potentially be a potent drug for cancer therapy.
What is Cordycepin?
Cordycepin is a naturally occurring nucleoside analogue also known as 3'-deoxyadenosine (or 3'-dA). Formerly it was extracted from the fungus named Cordyceps militaris but later it started being produced synthetically too. It is also found in other Cordyceps species as well as Ophiocordyceps sinensis. It attains anti-cancer, anti-oxidant, and anti-inflammatory effects.
Cordycepin Then and Now
Cordycepin is the active ingredient present in the engineered NUC-7738 extracted from the parasitic fungus species Ophiocordyceps sinensis (also known as caterpillar fungus because it kills and mummifies moth larva), used as a herbal remedy in traditional Chinese medicine for centuries.
Through the analysis of this nucleotide analogue, a chemotherapy drug was obtained and it has been revealed that it attained a potent anti-cancer agent and may in the future provide a new treatment option for patients with cancer. Now, the researchers at the University of Oxford have come to the point where the phytochemical can be supercharged and its anticancer potency can be boosted by up to 40 folds.
NUC-7738
To multiply cordycepin's potential as an anticancer agent, NUC-7738 makes use of several engineered advantages: it allows it to enter cells independently of nucleoside transporters, such as Human Equilibrative Nucleoside Transporter 1 (hENT1).
Unlike naturally occurring cordycepin, NUC-7738 doesn't rely on hENT1 to gain access to cells, and other tweaks to the molecule mean it's pre-activated (bypassing the need for the enzyme adenosine kinase), and is also resistant to breaking down in the bloodstream, with built-in protection against ADA.
Cordycepin in Cancer Therapy
Cordycepin has displayed cytotoxicity against some leukemic cell lines in vitro, and at least one clinical trial of cordycepin as a leukemia treatment is in progress. It has been found to produce rapid, robust imipramine-like antidepressant effects in animal models of
depression, and these effects, similarly to those of imipramine, are dependent on the enhancement of AMPA receptor signaling.
Early results from the first in-human clinical trial of NUC-7738 appear to be positive so far too. The Phase 1 trial, which began in 2019 and is still ongoing, has so far involved 28 patients with advanced tumors that were resistant to conventional treatment.
So far, weekly escalating doses of NUC-7738 given to this cohort have been tolerated well by the patients, who have shown "encouraging signals of anti-tumor activity and prolonged disease stabilization", the researchers report in their paper.
"These findings provide proof of concept that NUC-7738 overcomes the cancer resistance mechanisms that limit the activity of 3'-dA and support the further clinical evaluation of NUC-7738 as a novel cancer treatment." While it's certainly a promising start, it will still be some time before NUC-7738 becomes available to patients outside the trial.
Silent Pros
As Cordycepin is almost similar to deoxyadenosine nucleotide(3-dA) some of the enzymes find difficulties in differentiating between these two. Hence in some way, it helped in certain biochemical reactions by acting as an adenosine analog. For instance, 3-dA can trigger the Premature Termination Codons(PTCs) of mRNA synthesis which leads to the incorrect termination of translation and generation of non-functional, truncated proteins. This type of translational readthrough of PTCs induced by pharmaceutical compounds is a promising way of restoring functional protein expression and reducing disease symptoms, without affecting the genome or transcriptome of the patient.
In the same way, Cordycepin was found to be the most potent molecular circadian clock resetter out of several screened compounds.
Drawbacks
This naturally occurring Cordycepin extracted from O. sinensis ( Himalayan fungus) also has some drawbacks. It could be broken down quickly in the bloodstream – with a half-life of
1.6minutes in plasma – by the enzyme adenosine deaminase, or ADA. It resulted in
showing poor uptake into cells, meaning the molecule's actual potency against tumor cells in the body is greatly diminished.
References:
Comentários