3 replies
May '17

amritamallick00

Is it not normal to think, that maybe aspirin kills normal cells too. How is aspirin capable of distinguishing cancerous cells to normal cells? And if it can’t isn’t it dangerous to use aspirin in daily life?

1 reply
Jun '17 ▶ amritamallick00

van_shikha

Hi Amrita, that is indeed a thoughtful question. However, the researchers have clearly showed that upon aspirin treatment, the cell viability of normal oral mucosal cells remains intact, whereas that of cancer cells decreases (Refer Fig 1.1 in the link to the paper). The rationale behind this is the mechnaism of aspirin’s action against cancer, as explained in the Scientific Reports article and the news piece. I’ll explain it in greater detail here.

The site of action of aspirin is VDAC, a protein on the membrane of mitochondria. Hexokinase is the enzyme that is produced in excess in cancer cells to increase their metabolism. The enzyme binds to VDAC in the cancer cells, whereas for the normal cells, it remains in the cytoplasm. Since aspirin brings down the elevated metabolism of cancer cells by dissociating hexokinase from the mitochondrial VDAC, there is no chance of the normal cells getting affected, simply because the hexokinase that the aspirin acts on is in a different location than its site of action.

Hope I was able to resolve your query. Let us know if you have more questions.

Jan '18

tarunbiochem

Following on the discussion, I want to clarify here, that aspirin is not a specific drug against any single protein or other biomolecules. It has ability to chemically modify many proteins on their residues susceptible to acetylation both inside and outside a cell. After ingestion, aspirin is absorbed and hydrolyzed in blood stream and circulates and have been shown to even acetylate serum albumin and fibrinogen, though the half life of the drug is very short. Inside cells its well known targets are COX-1 and COX-2, which catalyze formation of proinflammatory molecules, and the major site of action of aspirin as antiinflammatory agent. There are other enzymes shown to be acetylated and inhibited by aspirin, like mutant p53, which is key target in cancers. The details about mechanism can be found here - https://www.nature.com/articles/bjc2014271 (Its not my paper).
Having said this, aspirin might be affecting VDAC too, but there is no evidence I could find in literature which shows that VDAC gets acetylated by aspirin. Though, VDAC has been shown in this Sc Rep paper to be affected by aspirin in vitro in cancer cells, which is interesting to be followed further.
To Amrita’s question, Yes it is well established that consuming aspirin (even at low dose) daily is risky for healthy individuals because of its prolonged antiplatelet action, thats why it is only given to cardiovascular patients and to some cancer patients these days.