13 replies to this topic

[maxwatt]

I came across this by accident, but it appears that the effect of substances that inhibit telomerase such as curcumin, and likely other inhibitors such as resveratrol, can be blocked by N-acetyl cysteine. It is possible that taking NAC with a telomerase activator could increase its effectiveness. If not directly, than by blocking the inhibitory effects from curcumin, resveratrol and substances found in a normal diet.

Mutat Res. 2010 Jun 1;688(1-2):72-7. Epub 2010 Apr 2.
N-acetyl cysteine mitigates curcumin-mediated telomerase inhibition through rescuing of Sp1 reduction in A549 cells.
Hsin IL, Sheu GT, Chen HH, Chiu LY, Wang HD, Chan HW, Hsu CP, Ko JL.

Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan, ROC.
Abstract
Curcumin is a natural compound that has been extensively observed due to its potential as an anticancer drug. Curcumin restrains cancer cell progression via telomerase activity suppression. However, the exact mechanism is still unknown. In this study, we demonstrate that the effects of curcumin on cell viability and telomerase activity can be blunted by reactive oxygen species (ROS) inhibitor N-acetyl cysteine (NAC). The ROS induced by curcumin in A549 cells was detected by flow cytometry. Using Western blot and RT-PCR, human telomerase reverse transcriptase (hTERT) decreased in the presence of curcumin. Sp1 is one of the important transcription factors in hTERT expression. Our data showed that curcumin decreases the expression of Sp1 through proteasome pathway. In addition, NAC blunted the Sp1 reduction and hTERT downregulation by curcumin. Further, reporter assay and DNA affinity precipitation assay confirmed the influence of curcumin on Sp1 in hTERT regulation. This is the first study to demonstrate that curcumin induces ROS production resulting in Sp1 binding activity inhibition and hTERT downregulation.

Copyright 2010 Elsevier B.V. All rights reserved.
PMID: 20363232

[JKDC]

Was that in cancer cells? Healthy natural substances have totally different effects in normal cells as opposed to cancer cells. I don't believe I found any pro-oxidant studies on normal cells from curcumin, reveratrol etc. which is what telomerase activators are supposed to help. That's why I think it is too early to recommend not taking curcumin while taking a telomerase activator since these studies are based on abnormal cells. It is possible that telomerase activators will help to increase telomerase in healthy cells while curcumin, resveratrol, green tea etc. prevent any theoretical increased cancer risk form taking them. Since the activators are so expensive I imagine they err on the side of caution. But it's good to have NAC to make glutathione in either case.

[realtimedyno]

I'm searching for anything connecting the advisability of combining curcurmin --I take about 6 grams daily--and NAC, considering the telomerase inhibitory and activating properties, respectively. I have been diagnosed with a cancer of unknown primary, and am self-treating with a variety of supplements. There is also telomere implications for carnosine. It is a point well taken that cancer cells and normal cells behave differently. However, I would loathe to be loading up on a telomerase inhibitor, an then find that it is cancelled out by NAC and/or carnosine. Of course, all these substances have multiple positive effects on the body, telomerase activity being only one benefit.
BTW, my general vitamin supplement from Life Extension Foundation contains 600 mg. of NAC. I therefore at least take curcurmin in the PM and the vitamin in the PM...don't know if this makes a difference.

[triplecrown]

I'm searching for anything connecting the advisability of combining curcurmin --I take about 6 grams daily--and NAC, considering the telomerase inhibitory and activating properties, respectively. I have been diagnosed with a cancer of unknown primary, and am self-treating with a variety of supplements. There is also telomere implications for carnosine. It is a point well taken that cancer cells and normal cells behave differently. However, I would loathe to be loading up on a telomerase inhibitor, an then find that it is cancelled out by NAC and/or carnosine. Of course, all these substances have multiple positive effects on the body, telomerase activity being only one benefit.
BTW, my general vitamin supplement from Life Extension Foundation contains 600 mg. of NAC. I therefore at least take curcurmin in the PM and the vitamin in the PM...don't know if this makes a difference.

Kind of a off the subject question but were you taking any supplements before being diagnosed with cancer? Or did you you start taking the curcumin and lef multi after being diagnosed?

Thanks,
Have a great day:)

Edited by triplecrown, 31 December 2010 - 10:16 AM.

[DorianGrey]

Xiao Z, Zhang A, Lin J, et al. Telomerase: a target for therapeutic effects of curcumin and a curcumin derivative in aβ1-42 insult in vitro. PLoS One. 2014 Jul 1;9(7):e101251.

 

These guys say that Cur1 (Curcumin without methoxy groups) and to a lesser extent the cheaper Curcumin at micromolar levels activate telomerase. "The curcumin concentrations in these studies (25 µmol/L-50 µmol/L) were far higher than in our study (10 µmol/L); "

 

"Curcumin and Cur1 both protected SK-N-SH cells from Aβ1–42 and up-regulated the expression of hTERT. " - so Curcumin may protect against amyloid plaques.

 

If true, that's quite something and all this "Curcumin is a Telomerase inhibitor" talk here in the forum would be B.S. that only applies to cancer cells.

[blood]

I have been diagnosed with a cancer of unknown primary, and am self-treating with a variety of supplements...

Sorry to hear of your cancer diagnosis.

Out of curiosity - have you been offered any 'mainstream' medical treatments for your cancer? Just wondering why you have chosen to self-treat?

Edited by blood, 23 July 2014 - 09:53 PM.

[niner]

Xiao Z, Zhang A, Lin J, et al. Telomerase: a target for therapeutic effects of curcumin and a curcumin derivative in aβ1-42 insult in vitro. PLoS One. 2014 Jul 1;9(7):e101251.

 

These guys say that Cur1 (Curcumin without methoxy groups) and to a lesser extent the cheaper Curcumin at micromolar levels activate telomerase. "The curcumin concentrations in these studies (25 µmol/L-50 µmol/L) were far higher than in our study (10 µmol/L); "

 

"Curcumin and Cur1 both protected SK-N-SH cells from Aβ1–42 and up-regulated the expression of hTERT. " - so Curcumin may protect against amyloid plaques.

 

If true, that's quite something and all this "Curcumin is a Telomerase inhibitor" talk here in the forum would be B.S. that only applies to cancer cells.

 

I've not read the paper, but the concentration ranges they're talking about (10-50 uM) would be pretty much impossible to reach in vivo.   If the telomerase in a cancer cell has become constitively activated (stuck in the "on" position) in a cancer cell due to a mutation, it's a different animal than normal telomerase in a healthy cell.   It might be the case that curcumin has an effect on telomerase in normal cells, but it's not obvious what the effect would be at achievable concentrations. 
 

[DorianGrey]

 

Xiao Z, Zhang A, Lin J, et al. Telomerase: a target for therapeutic effects of curcumin and a curcumin derivative in aβ1-42 insult in vitro. PLoS One. 2014 Jul 1;9(7):e101251.
 
These guys say that Cur1 (Curcumin without methoxy groups) and to a lesser extent the cheaper Curcumin at micromolar levels activate telomerase. "The curcumin concentrations in these studies (25 µmol/L-50 µmol/L) were far higher than in our study (10 µmol/L); "[/size]
 
"Curcumin and Cur1 both protected SK-N-SH cells from Aβ1–42 and up-regulated the expression of hTERT. " - so Curcumin may protect against amyloid plaques.[/size]
 
If true, that's quite something and all this "Curcumin is a Telomerase inhibitor" talk here in the forum would be B.S. that only applies to cancer cells.[/size]

 
I've not read the paper, but the concentration ranges they're talking about (10-50 uM) would be pretty much impossible to reach in vivo.   If the telomerase in a cancer cell has become constitively activated (stuck in the "on" position) in a cancer cell due to a mutation, it's a different animal than normal telomerase in a healthy cell.   It might be the case that curcumin has an effect on telomerase in normal cells, but it's not obvious what the effect would be at achievable concentrations.

 

 
I've read the paper a second time looking for hTERT upregulation in more detail and found this statement:
"We propose that curcumin and Cur1 have no effect on hTERT up-regulation in normal cells." The finding were only for stressed cells (amyloid plaques).[/size]
Curcumin has been used as a stain for amyloid plaques as an early Alzheimer test (Retina cells are nerve cells, so you have a direct view into the brain this way).
At least it seems it's also not an inhibitor.
 
ps: I recently came along a new class of small molecule telomerase activators, AGS-499 and AGS-500 from Ben Gurion University. These are symmertical Triphenylamines, quite interesting stuff.

Edit: fixed broken attributions -niner

Edited by niner, 24 July 2014 - 09:08 PM.

[Logic]

Xiao Z, Zhang A, Lin J, et al. Telomerase: a target for therapeutic effects of curcumin and a curcumin derivative in aβ1-42 insult in vitro. PLoS One. 2014 Jul 1;9(7):e101251.
 
These guys say that Cur1 (Curcumin without methoxy groups) and to a lesser extent the cheaper Curcumin at micromolar levels activate telomerase. "The curcumin concentrations in these studies (25 µmol/L-50 µmol/L) were far higher than in our study (10 µmol/L); "[/size]
 
"Curcumin and Cur1 both protected SK-N-SH cells from Aβ1–42 and up-regulated the expression of hTERT. " - so Curcumin may protect against amyloid plaques.[/size]
 
If true, that's quite something and all this "Curcumin is a Telomerase inhibitor" talk here in the forum would be B.S. that only applies to cancer cells.[/size]

 
I've not read the paper, but the concentration ranges they're talking about (10-50 uM) would be pretty much impossible to reach in vivo.   If the telomerase in a cancer cell has become constitively activated (stuck in the "on" position) in a cancer cell due to a mutation, it's a different animal than normal telomerase in a healthy cell.   It might be the case that curcumin has an effect on telomerase in normal cells, but it's not obvious what the effect would be at achievable concentrations.

These guys (linked below)combined Curcumin, vitamin C, vitamin E and polyvinyl-pyrrolidone to form a complex that is soluble in water and present in concentrations of between 25 and 33ng/mL in blood.
http://www.ncbi.nlm....pubmed/24461029

This leads me to ask: How does one convert that number to uM/L??

[niner]

These guys (linked below)combined Curcumin, vitamin C, vitamin E and polyvinyl-pyrrolidone to form a complex that is soluble in water and present in concentrations of between 25 and 33ng/mL in blood.

http://www.ncbi.nlm....pubmed/24461029

This leads me to ask: How does one convert that number to uM/L??

 

You have to use the relation 368 g curcumin = 1 mole curcumin.  (368 g is called the "molecular weight" of curcumin.  The MW of anything is the weight in grams of a mole of it.)  Also use the definition of molarity: 1M = 1m/liter.

 

33ng/ml * (1e-9 g/ng) * (1 m / 368g) * (umole / 1e-6 m) * (ml / 1e-3 liter)  = 33/368 umole/liter = 0.09 uM

 

So at less than a tenth of a micromolar, that's pretty horrid.  Of course, unformulated curcumin is even more horrid, so it's relative.  Curcumin has really lousy bioavailability...

Edited by niner, 19 August 2014 - 05:52 PM.

[Logic]

These guys (linked below)combined Curcumin, vitamin C, vitamin E and polyvinyl-pyrrolidone to form a complex that is soluble in water and present in concentrations of between 25 and 33ng/mL in blood.
http://www.ncbi.nlm....pubmed/24461029

This leads me to ask: How does one convert that number to uM/L??

 
You have to use the relation 368 g curcumin = 1 mole curcumin.  (368 g is called the "molecular weight" of curcumin.  The MW of anything is the weight in grams of a mole of it.)  Also use the definition of molarity: 1M = 1m/liter.
 
33ng/ml * (1e-9 g/ng) * (1 m / 368g) * (umole / 1e-6 m) * (ml / 1e-3 liter)  = 33/368 umole/liter = 0.09 uM
 
So at less than a tenth of a micromolar, that's pretty horrid.  Of course, unformulated curcumin is even more horrid, so it's relative.  Curcumin has really lousy bioavailability...

Thx so much Niner
You have me doing some maths for the 1st time in ages!

I was really surprised that even this new stuff that looks so good in the graphs still has such crappy bioavailability!

Where do you find the molecular weight of Curcumin etc?

[niner]

Where do you find the molecular weight of Curcumin etc?

 

Back in the day, one might have had to compute it by multiplying the number of each type of atom in the molecule by its atomic weight, and summing that to get the molecular weight.  These days, it's sufficient to google "curcumin MW", or more generally, substance_name mw.  If you look up a substance in wikipedia, the various molecular parameters and properties are usually given in a box at the top right.

[normalizing]

i just dont understand those actual human trials with curcumin helping depression at all. it does have shitty bioavailability and the ones i tried claimed to have been enhanced to have better bioavailability (including with bioperine) and yet to this day i have failed to notice even the most slight of antidepressant action using various brands. ive actually felt more difference from stuff tested only on animals. i keep being shocked curcumind showing antidepressant qualities in not one or two but three human trials i have seen....

[MachineGhostX]

i just dont understand those actual human trials with curcumin helping depression at all. it does have shitty bioavailability and the ones i tried claimed to have been enhanced to have better bioavailability (including with bioperine) and yet to this day i have failed to notice even the most slight of antidepressant action using various brands. ive actually felt more difference from stuff tested only on animals. i keep being shocked curcumind showing antidepressant qualities in not one or two but three human trials i have seen....

 

Did you try Longvida?  Because none of the other ones demonstrate any free curcumin in the blood, certainly not in the brain.

 

I would think there are much better bioagents to be trying for an antidepressant effect, though!

 

Edited by MachineGhostX, 21 August 2014 - 12:35 AM.