Most of the researchers are wonder about the dual activity of the curcumin.How it is possible for a compound to act as antioxidant(in normal cells) and ROS producer(in cancer cells)?
Dear Rajesh,
interessting question! Curcumin is a typical (in vitro) antioxidant, that means that it is able to scavenge chemically produced radicals in a test tube. If you look at biological systems, time and concentration make big differences in the outcome of studies. It is known that curcumin is a typical michael acceptor, meaning that it can interact with the keap1/nrf2 transcrition pathway. Doing that, nrf2 travels within the nucleus of a cell and activates gene expression of antioxidant enzymes (the only antioxidants, nature took care off;)
So finally curcumin occurs as a pro-oxidant (or better michael acceptor) if you look shortly after intervention. Later nrf2 activates the antioxidant enzymes. Depending on the cell type this route(s) depend on concentration, time and genetic disposition.
You will find further literature searching pubmed for adaptive stress response, hormetins, hormetics michael acceptors and or nrf2.
Best
Marc
Dear Rajesh,
interessting question! Curcumin is a typical (in vitro) antioxidant, that means that it is able to scavenge chemically produced radicals in a test tube. If you look at biological systems, time and concentration make big differences in the outcome of studies. It is known that curcumin is a typical michael acceptor, meaning that it can interact with the keap1/nrf2 transcrition pathway. Doing that, nrf2 travels within the nucleus of a cell and activates gene expression of antioxidant enzymes (the only antioxidants, nature took care off;)
So finally curcumin occurs as a pro-oxidant (or better michael acceptor) if you look shortly after intervention. Later nrf2 activates the antioxidant enzymes. Depending on the cell type this route(s) depend on concentration, time and genetic disposition.
You will find further literature searching pubmed for adaptive stress response, hormetins, hormetics michael acceptors and or nrf2.
Best
Marc
Marc has a great explanation. I always remember the Vit E story in preventing cardiovascular disease or retinopathy of prematurity. The issue become that a potent antioxidant will become a pro-oxidant once it accept electron from ROS unless the elctron can be passed down to a lower potential antoixidant. It is very situation depenedent.
Dear Rajesh
To add more, i am here presenting you in attachment some more relvant information reagarding your query.
Curcumin mediates its apoptotic and anti-inflammatory activities through modulation of the redox status of the cell. Many of the positive benefits of curcumin are a consequence of its pro-oxidant effect on thiol groups which are inhibited by glutathione and n-acetylcsyteine.
Very interesting discussion. However, in my group we considered curcumin as an antioxydant especially by the modulation effect on neutrophil activation and inhibition of two main oxidant enzymes myeloperoxidase and NadphOx.
We carried out some preliminary measurements (not published) on the antioxidant activity of curcumin in mixtures with some pharmaceuticals. It is quite interesting that at higher temperatures curcumin behaves as a prooxidant. At lower temperatures it shows antioxidant effects.
Curcumin is an excellent antioxidant, radical scavenger and NOT a radical producer. It offers protection against oxidative stress.
Curcumin is antioxidant, under normal physiological conditions. However at other conditions,e.g. higher pH and / or Temp, it may work as pro-oxidant.
I read this discussion on curcumin with a lot of interest, yes, it is still not clear why curcumin is an antioxidant in normal cells while it is a pro-oxidant in tumor cells.
Curucmin as such does not produce ROS, rather it is an excellent free radical scavenger, therfore it is an antioxidant under conditions where oxidative stress is mediated by ROS.
In tumor cells, curucmin is selctively uptaken , therfore it is more bioavailable in tumors than in normal cells. Beacuse of this its ability to act as Michael acceptor with thiols like glutathione becomes an important process. In general these products of glutathione-curcumin conjugates are not reversible, and they may induce oxidative stress. However this is still not confirmed. The behaviour of hese conjugates may depend on tumor microenvironment, conditions, etc.!!!!
Curcumin activates all genes associated with antixoidant action. But it is the differential regulation in tumor to normal cells makes it a special molecule for tumors.
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