In my last post, I looked at the different mechanism of actions of 3 OTC drugs – Aspirin, Acetaminophen and Ibuprofen. Aspirin a drug discovered ~100 years ago and in use for more than 50 years is one of the most common OTC drugs used. Aspirin is reported to be an analgesic, anti-pyretic, anti-inflammatory and anti-platelet agent. Recently I read a few reports that discussed the role of Aspirin in the prevention of cancer (1,2,3,4). This was really intriguing, that such a widely used drug with so many uses could also play a role in prevention of cancer.
As shown in my last post, aspirin and targets the COX1 and COX2 proteins and inhibits the formation of prostaglandins. Aspirin is also known to target other proteins.
I looked up DistilBio to find the protein targets of Aspirin.
Query: aspirin > protein Run Query
The results are as below:
Aspirin targets 35 proteins. Besides the PGH1 (COX1) and PGH2 (COX2) proteins, aspirin also interacts protein kinase C, MAPK proteins, Interleukin 4, Integrins, Raf and HRas proteins.
I further modified the query to find the disease indications associated with these proteins.
Query: aspirin > protein > disease Run Query
Clicking on each facet shows us the number of results obtained – 27 proteins and 115 diseases. The number of proteins seems to have reduced from my previous search as the others may not have a disease associated with it. Selecting each protein displays the diseases associated with the protein and vice versa.
For example, PGH2 has 24 diseases associated with it like Alzheimers, Myocardial infarction, Osteoarthritis, Asthma, Cancers – Breast, Colorectal, Pancreatic, Renal cell carcinoma, Ovarian etc.
RASH (HRAS) has Bladder cancer, Costello syndrome, Noonan Syndrome and Thyroid Carcinoma, Hurthle cell associated with it.
I further extended the query to include the Biological processes associated with these proteins.
Query: aspirin > protein > disease Run Query > GO-biologicalprocess
Interestingly, the proteins targeted by aspirin play roles in wide range of processes like ERK1 & ERK2 cascade, Ras Protein signal transductions, Angiogenesis, Blood coagulation, cell proliferation, cyclooxygenase pathway, EGFR signalling, regulation of bone resorption to name a few. Some of these processes are known to play a role in the development of cancer (5,6,7). More analysis of the data might give us a better understanding of the processes involved which is beyond the scope of this post.
The exact mechanism of action of aspirin, apart from the COX pathway, is not yet known fully and new interactions of the drugs are being reported (8,9,10). Maybe I will come back to these in later posts. This definitely will be a drug to keep an eye on.
References:
- Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. (PMID:22440946)
- Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials (PMID: 22440947)
- Effects of regular aspirin on long-term cancer incidence and metastasis: a systematic comparison of evidence from observational studies versus randomised trials (PMID: 22440112)
- NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid is a potent inhibitor of colon cancer cell growth in vitro and in a xenograft mouse model. (PMID: 22366248)
- EGFR signaling in breast cancer: bad to the bone. (PMID: 20813200)
- Signaling pathways governing tumor angiogenesis (PMID: 22212932)
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Cell proliferation and cancer. (PMID:9810511)
- Antitumor effect of aspirin in glioblastoma cells by modulation of β-catenin/T-cell factor-mediated transcriptional activity. (PMID: 21721879)
- Aspirin induces apoptosis in human leukemia cells independently of NF-kappaB and MAPKs through alteration of the Mcl-1/Noxa balance. (PMID: 19936928)
- Aspirin induces apoptosis through the blockade of IL-6-STAT3 signaling pathway in human glioblastoma A172 cells. (PMID: 19595669)
