2189 replies to this topic

[Louis]

The original issue I brought up was: Permanently turning on hTERT can protect a cell from mitochondrial damage over many many replications, e.g. the 10,000th division has mitochondria as robust as the 1st cell in the lineage.

I first cited the Geron experiments as proof of concept that this can occur in vitro. In fact, Geron has telomerized cells that are still dividing for many years now without any significant signs of mitochondrial damage. I then offered the example of germ cells as proof of concept that this can occur in vivo. Obviously, a germ cell is more complicated than a somatic cell with hTERT turned on with a viral vector -- they're not going to behave exactly the same. You're focusing in on this side detail about germ cells that some small amount of damage does occur in the germ cells over an organism's lifetime. I don't disagree with this at all, if that's what you're looking for me to say here. Evolution probably did this intentionally to allow random variation to enter into the gene pool.

It doesn't change the fact that the in vitro experiments prove that permanently turning on hTERT can protect the mitochondria over many years of cell division in vitro. And it doesn't change the fact that germ cells (the only normal cell line in the human body with hTERT permannently turned on) do more or less the same thing in vivo -- probably allowing some small amount of damage to occur as a source randomness for the gene pool during the organisms lifetime -- but in the end completely reset themselves.

And I mentioned this issue of germ cells repairing any accumulated damage before the baby is conceived in my very first message. I never changed my position on that at all. You just keep leaving that sentence out of the portion of the message that you quote.

Edited by Louis, 30 January 2012 - 04:44 AM.

[Louis]

We should also be careful about our terminology here: I'm referring to germ cells with hTERT permanently turned on. This discussion really applies mainly to sperm cells.

Edited by Louis, 30 January 2012 - 04:53 AM.

[Anthony_Loera]

It's not that the damage doesn't occur when hTERT is turned on permanently. It's that the cells in this case are capable of activating their own internal mechanisms to protect against and repair the damage.

Whether this will happen in all cells in vivo if hTERT is turned on is extremely controversial. But it certainly does happen when hTERT is permanently turned on in a variety of cells in vitro. And it certainly happens in your germ cells.

From a layman's perspective, this is interesting, but still not proven in vivo, and whether or not it happens in all cells is controversial (your words).

I have yet to see links to all the studies, specially any en vivo studies on germ cell lines that certainly confirms your feelings. This thread is about providing links to studies that are helpful. Heck, even the 'smoking is good for you' thread had links to studies that a certain person tried to use as proof on his "theory".

Please post links to abstracts to move the conversation forward.

Thanks
A

Edited by Anthony_Loera, 30 January 2012 - 02:28 PM.

[maxwatt]

You guys are splitting hairs. Most mutations are deleterious. A few confer an advantage. Reproductive cells are protected, do not divide so fewer mutations, and there are some mechanisms relying on redundancy that ensure faithful and genetically young copies. But every now and then a mutation occurs. Usually not good but sometimes conferring an advantage. There are also epigenetic mechanisms involved, and I wouldn';t be surprised if one day feedback to the genes is demonstrated, but really.... This is not an argument about facts but about semantics.

[Louis]

You can refer to Michael Fossel's books for the appropriate scientific references on the Geron experiments I am referring to.

If someone wants me to repeat them here, I'll be glad to post them.

Edited by Louis, 30 January 2012 - 03:47 PM.

[Anthony_Loera]

I am a layman, i dont have access to the books... So yes, please repeat the references here.

Thanks
A

[GreenPower]

I am a layman, i dont have access to the books... So yes, please repeat the references here.

Thanks
A

I haven't read a book by him since he wrote "Reversing human aging", so if you have any suggestions on book by him would would appreciate it.

I have a few comments, thoughts and questions on the latest posts.
1. What is the link between damaged mitochondria and birth defects? I understand that the mitochondria is largely isolated from the human chromosomes by a set of membrane walls and they would therefore not affect the quality of the chromosomes that much, and therefore not cause birth defects. And on page 215 in the above mentioned book Fossel indicates that it would take quite a long time before internal damage in the mitochondria reach any significant levels.
2. I understand that the HeLa cell line has been around since 1920 (or 1950 if you count the donors death), due to telomerase being activated. Since then these cells have divided many more times than they would otherwise have been able to. If the damage done to the mitochondria during these cell divisions were significant, I assume the cell line wouldn't work by this time. I therefore suppose the damage done to the the mitochondria of these cells cannot be that large - or if telomerase is actually protecting the mitochondria of these cells, that it should also protect the mitochondria of our own cells.
3. If you are on a LCHF (Low Carb High Fat) diet, there would be much less glucosis for the mitochondria to process into ATP and thereby much less free radicals which would damage components of the cell. I therefore wonder if LCHF might not be beneficial to the general state of the cell, including the quality of the DNA of the chromosomes and the mitochondria? If true, I assume a calorie restriction diet might work in approximately the same way.
4. The LCHF-theory might be supported by the fact (New Scientist) that during cancer the mitochondria power plants shuts down due to lack of oxygen, and the cell instead switches to glycolysis as a means of producing energy. This would decrease the concentration of free radicals inside the cell and thereby cause less damage to the internal organs of the cell and allow it to replicate more times. This would also be a counterargument to telomerase having anything to do with reparing mitochondria in the HeLa cell line.
5. How would a "reset" of damaged DNA in the mitochondria occur? If it's damaged I assume there's no blueprint stored inside the cell which would could be used in order to correct damages to it?

[niner]

This business of telomerase protecting mitochondria needs more explanation. How is that supposed to work, anyway? What kind of damage does the ROS do to the mitochondria? Is the mitochondrial genome damaged, or other components? When the cell divides, what's the mechanism of mitochonrdrial replication? Maybe the mitochondria are damaged, but the mitochondrial genome isn't, and new mitochondria are made from scratch based on the genome. I really don't know, but I'm having a hard time imagining how constitutively active telomerase would help the mitochondria. Anyone up on these things?

[zorba990]

This business of telomerase protecting mitochondria needs more explanation. How is that supposed to work, anyway? What kind of damage does the ROS do to the mitochondria? Is the mitochondrial genome damaged, or other components? When the cell divides, what's the mechanism of mitochonrdrial replication? Maybe the mitochondria are damaged, but the mitochondrial genome isn't, and new mitochondria are made from scratch based on the genome. I really don't know, but I'm having a hard time imagining how constitutively active telomerase would help the mitochondria. Anyone up on these things?

My concern is also that the original cell is (possibly) having it's life cycle artificially extended. Maybe to the point where mitochondrial function completely stops, leaving the cell very vulnerable (from my understanding) to becoming cancerous. If the new divided cells have normal mitochondria then that's great. If turning on telomerase protects the mitochondria then that may solve the issue also. Just haven't seen any proof to this effect. I'm not sure it's worth activating telomerase if the risk is an increase in cancer possibility.

The HeLA are cancer cells and so, I thought, by definition have malfunctioning mitochondria (Warburg Effect) .

[Robert89]

I am starting to see the reasons why there is so much concern about switching telomerase on artifically could be unhealthy, ie in terms of tumour or cancer growth. Any malfunctions could not be discarded by the body (ie cell death) because the telomerase would be on all the time? Isn't this what Zorba 990 is saying?

I would also like to ask if there has been any published data that shows increased (1) life time (2) life quality of any mammals (mice, humans) or any other animals? From getting to know abut longevity these past couple of years, I've come to the understanding that the 'gold standard' is ACTUAL increased, demonstratable data. There doesnt seem to be any for TA65- Cycloastragenol.

TA Sciences have 3-4 years of human (customer) data and could have commissioned a mice study by now? How come there is no data that shows improvement over control subjects? (I am not counting the initial 'pilot human trial' because it's conclusions on NK cells was a direct opposite to their 3 year human trial with customers data later ... also the 2nd longer trial was not conclusive in any real definate way ... there were lots of trial design issues, ie. no double blind, no control group, etc. etc. The authors promised to provide data later, but they didn't.)

Anthony, since you're the official re-seller of TA65 on this forum, and have access to research resources and access to TA Sciences, what's your take on this? Why no data that shows animal model success in longevity with cycloastragenol / TA65? I searched on PubMed and couldn't find anything in vivo either.

If not animal studies with mice, then what about other animal models? If there is no data there to support cycloastragenol/ TA65, isn't that a bit strange?

[Anthony_Loera]

Hi Robert89,

You are right we do re-sell TA-65, however the information we have is the same public information available to you as well.

I understand that the last study done by Blasco shows no cancer issues:

The telomerase activator TA-65 elongates short telomeres and increases health span of adult/old mice without increasing cancer incidence
http://www.ncbi.nlm....pubmed/21426483

Here, we show that a small-molecule activator of telomerase (TA-65) purified from the root of Astragalus membranaceus is capable of increasing average telomere length and decreasing the percentage of critically short telomeres and of DNA damage in haploinsufficient mouse embryonic fibroblasts (MEFs) that harbor critically short telomeres and a single copy of the telomerase RNA Terc gene (G3 Terc(+/-) MEFs). Importantly, TA-65 does not cause telomere elongation or rescue DNA damage in similarly treated telomerase-deficient G3 Terc(-/-) littermate MEFs. These results indicate that TA-65 treatment results in telomerase-dependent elongation of short telomeres and rescue of associated DNA damage, thus demonstrating that TA-65 mechanism of action is through the telomerase pathway. In addition, we demonstrate that TA-65 is capable of increasing mouse telomerase reverse transcriptase levels in some mouse tissues and elongating critically short telomeres when supplemented as part of a standard diet in mice. Finally, TA-65 dietary supplementation in female mice leads to an improvement of certain health-span indicators including glucose tolerance, osteoporosis and skin fitness, without significantly increasing global cancer incidence.

A

[Louis]

CELLS, AGING, AND HUMAN DISEASE. Oxford University Press, 2004.
I would recommend Fossel's book above.

I'm sorry, I've been away on business travel and don't have access to my books/papers at home.
I'll post the references I promised when I get home this weekend.

In the meantime, I would recommend starting by reading the following seminal paper from Jerry Shay and Woodring Wright:

"Extension of life-span by introduction of telomerase into normal human cells."
Bodnar, A.G., M. Ouellette, M. Frolkis, S.E. Holt, C.P. Chiu, G.B. Morin, C.B. Harley, J.W. Shay, S. Lichtsteiner, and W.E. Wright , Science , 1998; (279/5349):349-352

This was the first publication of an experiment where a virus was used to insert an active telomerase gene into a normal (non-cancerous) human cell line in vitro.
It's probably the first key paper related to what we've been discussing here -- you can work your way forward through the literature by starting here.

Immortalized cells from the Shay/Wright lab are still dividing in petri dishes all over the world. In fact, you can purchase them for experiments, e.g. many labs use them in cancer research. But they're not cancer cells -- they're perfectly healthy human cells with an active copy of hTERT inserted via a virus. They have very healthy and robust mitochondria, despite many years of cell division.

[niner]

I am starting to see the reasons why there is so much concern about switching telomerase on artifically could be unhealthy, ie in terms of tumour or cancer growth. Any malfunctions could not be discarded by the body (ie cell death) because the telomerase would be on all the time?

Telomerase activators don't cause telomerase to be on all the time, they just cause it to be expressed a little more. If you stop taking the activator, that process would also stop. While the cancer concern was reasonable, it appears to be the case in the various human and animal studies that cancer rates are not increased.

Anyone looking for a large increase in longevity in any animal (including humans) will probably be disappointed, unless that animal was modified in some way such that they have abnormally short telomeres but still have normal telomerase genetics. I expect telomerase activators to be a step forward in terms of increased healthspan, probably some curve squaring, and possibly a small increase in Max LS. I hope I'm wrong, and that it's a lot more than that, but at this point, I think the dreams of hugely increased lifespans are just that. Time will tell, at any rate.

[Robert89]

OK, thanks guys. Those links and extra information were helpful to me to get my head around telomerase expression. It seems that there is some mild benefit to be had with cycloastragenol use, but nothing like the hype we were seeing from a couple of years ago ... where words like "immortal cell lines" were being banded about as if that might actually be possible.

The benefits of cycloastragenol are actually similar to something Alpha lipoic acid (ALA), which gives similar or not better characterised lab data showing animal models such as mice, actually having an increased lifespan, and a whole bunch of health/ longetivity indicators. (source: Wiki) However, ALA can be had for 20 USD for a huge bottle that will last 2-3 months, whereas cycloastragenol costs much much more.

Currently I am on the same regime as Greenpower, with the gingko biloba with the raw astragalus extract, meditation and excercise ... it seemed to elongate his telomeres considerably, but the cycloastragenol by itself didn't.

[Louis]

I doubt you'll ever see a telomerase activator have much effect on mouse lifespan. Mice don't age telomerically. They die with very long telomeres.
(There's some evidence that telomere length plays a minor role in the second year of a mouse's lifespan, but the effect is small.)

Most of the mouse telomerase experiments have been with knockout mice where telomerase is permanently shut off. The knockout mice then behave much more like humans and age telomerically, i.e. telomere length becomes a critical path in their aging. But these experiments are artificial.

Lack of an appropriate short-lived model organism and a strong-enough telomerase activator are the major reasons why there's no data either way on telomerase and life extension in a real animal. No one's been able to do the experiment yet. The question is really indeterminate at this point.

Recently there was a very interesting paper published on Zebra Finches (birds), showing a strong correlation between age and telomere length. It looks like these finches may be the first good short-lived model organism for an experiment. All that's missing now is a strong activator. But in the meantime, feeding TA-65 to zebra finches would make for an extremely interesting experiment.

Edited by Louis, 02 February 2012 - 04:36 AM.

[Louis]

In case you're interested in feeding TA-65 to your pet zebra finch:
http://www.pnas.org/...3.full.pdf html

(This is a PDF of the full paper.)

[Louis]

This business of telomerase protecting mitochondria needs more explanation. How is that supposed to work, anyway? What kind of damage does the ROS do to the mitochondria? Is the mitochondrial genome damaged, or other components? When the cell divides, what's the mechanism of mitochonrdrial replication? Maybe the mitochondria are damaged, but the mitochondrial genome isn't, and new mitochondria are made from scratch based on the genome. I really don't know, but I'm having a hard time imagining how constitutively active telomerase would help the mitochondria. Anyone up on these things?

Niner, the best data on the connection between telomeres/mitochondria so far comes from the recent DePinho mouse study.

From a press release:

As telomeres—protective caps at the end of cell chromosomes—shorten with age and begin to fray, cells activate the p53 gene, which signals an “emergency shutdown” chain of events that turns off normal cell growth and division and compromise antioxidant defenses. Going one step further, data from the carefully orchestrated mouse study, published in Nature, showthat the p53 gene also represses PGC1-alpha and PGC1-beta. These PCGs are considered the master regulators of metabolism and mitochondrial function.

Repressing PCGs increases the number of dysfunctional mitochondria (with mutated mitochondrial DNA) and leads to a decrease in functional mitochondria distributed throughout in muscles and organs. The dysfunctional mitochondria in aged tissues leak greater amounts of reactive oxygen species and the lack of functional mitochondria hinders normal energy production from cell respiration (the body’s main producer of ATP energy).

“What we have found is the core pathway of aging connecting several age-related biological processes previously viewed as independent from each other,” said Ronald A. DePinho, M.D., a cancer geneticist and senior author of the paper, in a press release.

[AdamI]

Telomeres in mice don't affect there lifespan? There is studies that say that...

"
At Harvard, they bred genetically manipulated mice that lacked an enzyme called telomerase that stops telomeres getting shorter. Without the enzyme, the mice aged prematurely and suffered ailments, including a poor sense of smell, smaller brain size, infertility and damaged intestines and spleens. But when DePinho gave the mice injections to reactivate the enzyme, it repaired the damaged tissues and reversed the signs of ageing.
"These were severely aged animals, but after a month of treatment they showed a substantial restoration, including the growth of new neurons in their brains," said DePinho."
http://www.guardian....ing-mice-humans

Or have I missed something? They do write:
Although this is a fascinating study, it must be remembered that mice are not little men, particularly with regard to their telomeres, and it remains unclear whether a similar telomerase reactivation in adult humans would lead to the removal of senescent cells."

[romtm]

Hi.I am new on this forum,but I read all the posts here (54 pages).I am 50 years old, live in Europe, and I decided ,two months ago,to folow the anti-aging supplements recomandations from the book "The Immortality Edge", taking 10mg/day of cycloastragenol instead of TA-65.

Looking for a lower cost replacement for TA-65,I found a new Telomerase Activator, and a new anti-aging Protocol,claimed to be better than Patton protocol,with faster results

I am interested about the opinions of anyone on this forum regarding of this Telomerase Activator/Protocol.

The Telomerase Activator is called REVITAL-TA,and is produced by Canadian company Provita-nutrition.com. It cost only 60 USD/60 capsules and please look to the ingredients:

KÖNIG REVITAL-TA™
Telomerase Activator
60 ACID RESISTANT CAPSULES

MEDICINAL INGREDIENTS:

TA-100S (SM Cycloastragenol Sulphate).............................................................5 mg

Astragaloside IV..................................................................................................25 mg

Colostrum 30% IgG.............................................................................................50 mg

Saccharomyces Cerevisiae extract (P43).............................................................10 mg

L-Carnosine..........................................................................................................35 mg

L-Histidine............................................................................................................55 mg

L-Alanine..............................................................................................................55 mg

L-Glutamine.........................................................................................................55 mg

L-Glycine..............................................................................................................55 mg

Aspartic Acid........................................................................................................45 mg

Placenta extract ....................................................................................................25 mg

Nucleic Acid (RNA).............................................................................................25 mg

Astragalus membranaceus 20:1 PE....................................................................250 mg

Here are the GERONTOVERSAL protocol.

Telomerase Activator: day 1-21(3 weeks)
-morning:NADH
-evening: Stemulin (Stem Cell Activator), Q10
Revital-TA
HGH activator

Telomerase Inhibitor:day 22-28(1 week)
-Resveratrol Synergistic
-Serra Plus
-Super Immune
-Foo Ti Teng
-Quercetin
And,of course,general testing plus Telomer testing before and after 6 months of using the Protocol.

The manufacturer claim that GERONTOVERSAL protocol have faster results compared with Patton Protocol and that Revital-TA,with main component TA-100S,have better results compared with TA-65.

Also,Provita claim that their protocol:

1) activates cyclically the enzyme telomerase for repairing ADN of telomers responsible for maintaining youthful cells
2) Enable the production of stem cells to regenerate organs and immune cells
3) modulates the immune system
4) Increase energy production at cell level (especially brain and heart)
5) Eliminates inflammation at the cellular level and tissue
6) Block cyclically telomerase with anti-tumor effect

More details on their website.

Anyway,the 60 USD price for one month supply of this Telomerase Activator- that contain cycloastragenol,astragaloside,astragalus and more-is very interesting.

I appreciate any opinion.

[AdamI]

My 1st thought is, how in the world can one capsule only cost a dollar? One capsule contains 5 mg of Cyclo and 25mg of AIV.
Those two components are very expensive, dunno about the rest in costs... how are they able to sell it that cheap?! Unless it's fake?

[romtm]

I am buying Cycloastragenol, bottle with 60 capsules at 10 mg/ 98% purity with 115 USD,this means more or less 1 USD/capsule of 5 mg Cyclo.Bulk Cyclo is much cheaper and the manufacturer who put in capsules and bottles make a huge profit(300-1000%).Astragaloside is contained in astragalus extract (10% astragaloside)-and in this low concentration is cheap.

[AdamI]

Well then give me the link to that place where cyclo is that cheap, plz:)
But you might be correct still this was my 1st thought.
Don't find any info on where they state it's better than TA-65 though. A link would be nice there as well if you have any.

[romtm]

Go to amazon.com and make a search for Cycloastragenol.You can expect 20-30% discount for 3-5 bottles.On the page you will see 2-3 other seller with all details.Are chinese manufacturers.

For the info requested about Revital-TA and the main incredient TA-100S-I have in my language,I must look for one in english.

[Anthony_Loera]

One things for sure...

I definitely don't think they need to fear their trademark name being stolen...
Also, be careful, as we have had issues in Romania and counterfeiting of products in that area.

A

Edited by Anthony_Loera, 02 February 2012 - 03:37 PM.

[romtm]

Anthony,

I just spoke with romanian distributor of Provita Nutrition.They told me that the President is a romanian guy, Ph.D Lucian-Bogdan Delcea, that live in Canada for many years and all the products are manufactured in Canada, under GMP and QCMS standards. I will call him myself.Anyway,is always a risk that inside of a capsule is something else like advertised on the label.

Maybe you have an idea how to check in Canada if they really are selling what are advertising?

[Louis]

Telomeres in mice don't affect there lifespan? There is studies that say that...

"
At Harvard, they bred genetically manipulated mice that lacked an enzyme called telomerase that stops telomeres getting shorter. Without the enzyme, the mice aged prematurely and suffered ailments, including a poor sense of smell, smaller brain size, infertility and damaged intestines and spleens. But when DePinho gave the mice injections to reactivate the enzyme, it repaired the damaged tissues and reversed the signs of ageing.
"These were severely aged animals, but after a month of treatment they showed a substantial restoration, including the growth of new neurons in their brains," said DePinho."
http://www.guardian....ing-mice-humans

Or have I missed something? They do write:
Although this is a fascinating study, it must be remembered that mice are not little men, particularly with regard to their telomeres, and it remains unclear whether a similar telomerase reactivation in adult humans would lead to the removal of senescent cells."

Those are the DePinho mouse experiments I was referring to.

These are knockout mice. They were genetically engineered with telomerase off, but with the ability to turn in back on using a drug. This is all artificial. These are not real mice. With telomerase off, the mice lived considerably shorter lives than real mice. But when turned back on, their lifespan again approached normal and much of their premature aging was reversed (but they lived no longer than normal mice).

It's definitely not proof that telomerase can extend lifespan in a real animal.

[johnross47]

I am currently using astragalus extract while waiting for Anthony's new product, and hoping it will be within budget, (Astral Fruit was only just within budget) but even on a one week on, one week off regime I have increasing insomnia through the on week, which gradually goes after two days off. In the on week I also have extremely vivid and complicated dreams, and those fade to normal in the off week. By the end of the on week the dreams have got to the point where my sleep has become extremely "noisy" with long periods of repetitive images and phrases instead of more coherent dreams. ( if any dream could be called coherent.....my usual dreams do at least feature a series of discreet events in some sort of sequential story) Has anyone else experienced this? I don't recall it happening on cycloastragenol to anything like this degree.

[johnross47]

Yunjiu Cheng^#, Kai Tang^#, Suhua Wu^*, Lijuan Liu, Cancan Qiang, Xiaoxiong Lin, Bingqing Liu

Abstract Top

To determine the efficacy and underlying mechanism of Astragalus polysaccharides (APS) on plasma lipids in hypercholesterolemia hamsters. The effect of APS (0.25g/kg/d) on plasma and liver lipids, fecal bile acids and neutral sterol, cholesterol absorption and synthesis, HMG-CoA reductase activity, and gene and protein expressions in the liver and small intestine was investigated in twenty-four hypercholesterolemia hamsters. Treatment periods lasted for three months. APS significantly lowered plasma total cholesterol by 45.8%, triglycerides by 30%, and low-density lipoprotein-cholesterol by 47.4%, comparable to simvastatin. Further examinations revealed that APS reduced total cholesterol and triglycerides in the liver, increased fecal bile acid and neutral sterol excretion, inhibited cholesterol absorption, and by contrast, increased hepatic cholesterol synthesis and HMG-CoA reductase activity. Plasma total cholesterol or low-density lipoprotein-cholesterol levels were significantly correlated with cholesterol absorption rates. APS up-regulated cholesterol-7α-hydroxylase and LDL-receptor gene expressions. These new findings identify APS as a potential natural cholesterol lowering agent, working through mechanisms distinct from statins.

[johnross47]

http://www.plosone.o...al.pone.0027437

full text of the article here.

[johnross47]

RESEARCH ARTICLE Year : 2012 | Volume : 44 | Issue : 1 | Page : 78-81
Anti-tumor effects of Astragalus on hepatocellular carcinoma in vivo

Lian-Kun Li¹, Wen-Juan Kuang², Yun-Feng Huang¹, Han-Hong Xie¹, Guo Chen¹, Qing-Chun Zhou¹, Bin-Rong Wang¹, Li-Hong Wan^2
1 Department of Medicine, Sichuan General Hospital of Armed Police Force, Chengdu, Sichuan, China
² Department of Pharmacology, West China Center of Medical Sciences, Sichuan University, Chengdu, Sichuan, China
Date of Submission 20-Jan-2011 Date of Decision 03-Oct-2011 Date of Acceptance 18-Oct-2011 Date of Web Publication 14-Jan-2012

Correspondence Address:
Li-Hong Wan
Department of Pharmacology, West China Center of Medical Sciences, Sichuan University, Chengdu, Sichuan
China

DOI: 10.4103/0253-7613.91872


» Abstract
Objective: The objective of the present study is to investigate the anti-proliferation activity of Astragalus on human hepatocellular carcinoma (HCC) cells and its mechanism. Materials and Methods: Hepatic cancer H22 bearing mice were used to study the anti-hepatocarcinoma activity of Astragalus in vivo. The growth curve and inhibitory rate of tumor growth were measured. Cell apoptosis of each group was measured by flow cytometry (FCM). Protein expression of Bax and Bcl-2 were analyzed by immunohistochemistry (IHC). The Statistical Package for Social Sciences version 13.0 (SPSS Inc, Chicago, IL) was used for standard statistical analysis including one-way ANOVA and Student's t-test. A value of P<0.05 was considered to be statistically significant.
Results: Astragalus significantly inhibited the growth of H22 carcinoma, with an inhibitory rate of 17.28-52.36%. FCM and immunohistochemical assay show that the cell apoptosis rate and protein expression of Bax and Bax/Bcl-2 ratio of H22 transplanted tumor inAstragalus treated group were significantly higher than the control group (P<0.05). The protein expression of Bcl-2 was significantly lower than control (P<0.05).
Conclusion: The results of the present study suggest that Astragalus has significant anti-tumor effect in vivo in inducing apoptosis of H22 tumor cells by promoting protein expression of Bax, decreasing protein expression of Bcl-2 gene, and markedly increasing the Bax/Bcl-2 ratio.