Posted on 05/28/2011 9:44:31 AM PDT by neverdem
Scientists in the UK have moved a step closer to understanding how ibuprofen could help treat cancer. The findings could lead to the drug being used as a preventative treatment for prostate cancer, in the future.
Ibuprofen - a common painkiller - can help reduce the risk of prostate cancer, but the mechanism by which it inhibits tumour cells is still not fully understood. Now, Matthew Lloyd and his team from the University of Bath in the UK, in collaboration with Cancer Research UK, have uncovered a mechanism suggesting that the chiral inversion of ibuprofen inhibits the activity of the protein alpha-methylacyl-CoA racemase (AMACR), levels of which are increased in the presence of prostate, some colon and other cancers.
Lloyd explains that AMACR catalyses the chiral inversion of 2-methyl-fatty acyl-CoA esters, which are thought to be related to tumour cell growth. 'We would like to produce a chemical that binds really tightly to the protein [AMACR] and stops it working, because that would be a potential treatment for prostate cancer,' he says.
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Ibuprofen's R-enantiomer binding to the protein AMACR, which converts it into the active S-enantiomer
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The team decided to study whether AMACR would catalyse the chiral conversion of ibuprofen from its R-enantiomer to its S-enantiomer (the active species that is used to treat inflammation) instead of catalysing the chiral conversion of 2-methyl-fatty acyl-CoA esters, thus resulting in a chemopreventive effect.
First they converted a racemic mixture of ibuprofen into its coenzyme A ester to make a substrate for the AMACR to bind to. They then observed that the R-enantiomer of the ibuprofen-CoA ester bound tightly to the AMACR, resulting in 50 per cent being converted to the S-enantiomer - this involves removal of the R-ibuprofen alpha-proton followed by non-selective reprotonation.
The cycle was repeated, so that you end up with a net conversion of R to S. Lloyd explains that the significance of the finding is that while AMACR is doing the chiral conversion of ibuprofen, it is not able to promote cancer growth. In addition, the net conversion of R-ibuprofen to the active S-ibuprofen means that all of the drug can be used for its inflammatory effect.
'The fact that the AMACR is able to convert the R-ibuprofen into S-ibuprofen is not new, but it has never really been demonstrated before that this is a general phenomenon that applies to several of the drugs in the same class,' says Aurelie Courtin, a drug development expert at the University of Cambridge, UK. However, she indicates that at present ibuprofen cannot be used as a preventative treatment for cancer. 'Further experiments are needed to prove its anticancer effect; in vitro first on different cancer cell models and then in vivo. Furthermore, as it would be a long term treatment, it is important to study its toxicity - mainly on the liver - and its side effects,' she adds.
Lloyd agrees that ibuprofen should not be seen as a wonder drug just yet. 'There is still a long way to go and further work is definitely needed,' he says.
Chiral inversion of 2-arylpropionyl-CoA esters by human 
-methylacyl-CoA racemase 1A (P504S)—a potential mechanism for the anti-cancer effects of ibuprofen
Timothy J. Woodman, Pauline J. Wood, Andrew S. Thompson, Thomas J. Hutchings, Georgina R. Steel, Ping Jiao, Michael D. Threadgill and Matthew D. Lloyd, Chem. Commun., 2011
DOI: 10.1039/c1cc10763a
Wow. I am so glad to be on your ping list.
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My body doesn’t like Ibuprofen. I have two crazy symptoms when ever I try to take it. One, I feel my temperament change. About an hour after taking an Ibuprofen I become angry, agitated, and feel like I could beat my way out of a wet paper bag. I snap at anyone who even looks my way. And that’s not like me!
But I feel it. I feel it coming on. I feel myself changing from my normal ho hum temperament into a crazy screaming she witch from h e double L.
The second symptom is that the next day my bladder makes me go a tiny bit a thousand times a day and my urethra hurts really really bad when I urinate. And there is blood in my urine if I take Ibuprofen for more then one day.
Told my DH and he said: Sure it helps prostate issues, but it’ll put a hole in your stomach.” :o
Prostrate cancer may not be a threat to you?!
I don’t think that you have to worry about prostate cancer. >:-}
Perhaps this is the only good side effect of my herniated disk and surgery. I took so many ibuprofens to treat back pain that it possibly has caused me to have a rather low PSA. Currently I'm taking 800 mg 3 times a day to treat inflammation associated with plantars fasciatis.
Hmmmm
**Sure it helps prostate issues, but it’ll put a hole in your stomach.”**
Take it with food and you should be all right.
I had that, and got rid of it by getting fitted show inserts. A scanner measures the foot, and it takes about a week or so to get them. It will have a heel area raised on its circumference, and pocketed in the middle where the pain is. The rest of the insert is shaped to stop foot rotation as you walk. Some relief immediately, pain free in a few weeks.
oopps... show = shoe
BTW - me thinks you don't have to worry about prostate cancer ;>
Problem is....the stuff will eat your stomach up. Nearly killed me when I took it for pain. My stomach has never really recovered.
I’m being treated by a podiatrist right now. I wouldn’t be taking the prescription dose of ibuprofen without a physician’s prescription. I’m getting new orthotics, doing prescribed stretches and exercises for my feet, and had cortisone injections in my feet. Hopefully my feet will be healed in 3 months, and I will be able to resume more activities at that time. I have been told that it is not uncommon for people who have back pain or back surgery to also develop foot problems.
This may lower the cost of ibuprofen as well. You don't have to be concerned about packaging purified S-ibuprofen. The racemized mix of R and S versions has a beneficial effect when the R version is being converted to the S version. You still get all the inflammation relieving value of the S version. Folks who want the cancer restraining version as purified R-ibuprofen can pay a little extra for that step. There is no justification for purifying the S-ibuprofen version now.
How’s your kidney function?
I just had it tested, and it’s good.
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