Glucose deprivation activates feedback loop that kills cancer cells: study

Compared to normal cells, cancer cells have a prodigious appetite for glucose, the result of a shift in cell metabolism known as aerobic glycolysis or the "Warburg effect." Researchers focusing on this effect as a possible target for cancer therapies have examined how biochemical signals present in cancer cells regulate the altered metabolic state.

Now, in a unique study, a UCLA research team led by Thomas Graeber, a professor of molecular and , has investigated the reverse aspect: how the metabolism of glucose affects the present in cancer cells.

In research published June 26 in the journal Molecular Systems Biology, Graeber and his colleagues demonstrate that glucose starvation — that is, depriving cancer cells of glucose —activates a metabolic and signaling amplification loop that leads to cancer cell death as a result of the toxic accumulation of reactive oxygen species, the cell-damaging molecules and ions targeted by antioxidants like vitamin C.

The research, which involved UCLA scientists from the Crump Institute for Molecular Imaging, the Institute for Molecular Medicine, the California NanoSystems Institute, the Jonsson Comprehensive Cancer Center, the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, and the Department of Pathology and Laboratory Medicine, demonstrates the power of systems biology in uncovering relationships between metabolism and signaling at the network level.

"Most strikingly, our discovery that glucose withdrawal causes both cell death and increased tyrosine phosphorylation is intriguing because increased tyrosine kinase signaling is normally associated with cell growth," said Nicholas A. Graham, a senior postdoctoral scholar in Graeber's lab who helped design the project.

To explain the seemingly contradictory result that glucose deprivation reduced viability and at the same time increased signaling, the authors used an unbiased approach that included phospho-tyrosine mass spectrometry and other biochemical profiling techniques.

Assessing the "crosstalk" between metabolism and signaling, they discovered that the glucose deprivation activates a positive feedback loop whereby the withdrawal of glucose induces increased levels of reactive oxygen species, which in turn inhibit negative regulators of tyrosine signaling. The resulting supra-physiological levels of tyrosine phosphorylation then generate additional reactive oxygen species.

"Because live on the edge of what is metabolically feasible, this amplifying cycle of oxidative stress ultimately overwhelms and kills the cancer cell," Graeber explained. "These findings illustrate the delicate balance that exists between metabolism and signaling in the maintenance of cancer cell homeostasis."

In addition, the authors showed the possibility of exploiting this positive feedback loop for therapeutic intervention. Combining short-term glucose deprivation with an inhibitor of tyrosine phosphatases, they demonstrated synergistic cell death in a cancer cell line.

"Understanding the links between metabolism and signaling will empower new therapeutic approaches toward inducing this metabolic catastrophe," Graham said. "This study provides a framework for rational design of combinatorial therapeutics targeting both metabolism and signaling in cancer."

The findings by Graeber and his colleagues add to the emerging concept of systems integration between oncogenic signaling networks and the metabolism of malignant tumors. The work lays a foundation for future studies delineating how signaling and metabolism are linked, with the ultimate goal of refining therapeutic strategies targeting metabolism.

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PussyCat_Eyes
1 / 5 (2) Jun 26, 2012
This is a great breakthrough. Since Erythrocytes carry glucose in the hemoglobin to feed all the cells, it may help to isolate the cancer cells and establish stasis.
ziphead
4 / 5 (4) Jun 26, 2012
"Since Erythrocytes carry glucose in the hemoglobin to feed all the cells..."

Wow. This is new science to me. Literally.
PussyCat_Eyes
1 / 5 (1) Jun 28, 2012
Erythrocytes = red blood cells
TheGhostofOtto1923
4.6 / 5 (11) Jun 28, 2012
bloodletting = therapeutic phlebotomy
http://en.wikiped...ood_cell
ziphead
4 / 5 (4) Jun 29, 2012
"Erythrocytes = red blood cells"

The irony of the previous statement must have missed you by a mile; Erythrocyte/haemoglobin purpose is to carry oxygen (NOT glucose).

You should ask for refund from your community college.
PussyCat_Eyes
1 / 5 (2) Jun 29, 2012
And YOU should refrain from commenting on things of which you have no knowledge.
Apparently, you missed much in the article if you bothered reading it at all, or instead went directly to my comment. The article is about "glucose withdrawal and glucose deprivation in cancer cells". You seem to have a problem with comprehension skills just like Blotto. I can only assume that you have high regard for him and wish only to follow in his footsteps. Either that, or you are one of his many sock puppets. I fail to see the point of irony in a medical thread. You will never make it in the medical field. Try AGW.
TheGhostofOtto1923
4.6 / 5 (11) Jun 29, 2012
And YOU should refrain from commenting on things of which you have no knowledge.
Apparently, you missed much in the article if you bothered reading it at all, or instead went directly to my comment. The article is about "glucose withdrawal and glucose deprivation in cancer cells". You seem to have a problem with comprehension skills just like Blotto. I can only assume that you have high regard for him and wish only to follow in his footsteps. Either that, or you are one of his many sock puppets. I fail to see the point of irony in a medical thread. You will never make it in the medical field. Try AGW.
Uh you did say this didnt you?
Since Erythrocytes carry glucose in the hemoglobin to feed all the cells
-Yes or no?
You should ask for refund from your community college.
Not a problem - this lying imbecile gets his/her edumacation from buzzle.
TheGhostofOtto1923
4.7 / 5 (12) Jun 29, 2012
"Erythrocytes = red blood cells"

The irony of the previous statement must have missed you by a mile; Erythrocyte/haemoglobin purpose is to carry oxygen (NOT glucose).

You should ask for refund from your community college.
Yeah. And since no nurse would ever make this mistake we now have proof that the lying dimwit pussy/pirouette/ritchieguy/russkiye is no RN. Wow.
PussyCat_Eyes
1 / 5 (2) Jul 02, 2012
"Erythrocytes = red blood cells"

The irony of the previous statement must have missed you by a mile; Erythrocyte/haemoglobin purpose is to carry oxygen (NOT glucose).

You should ask for refund from your community college.
- ziphead

You seem to be so much smarter than actual researchers. Perhaps you are still not aware that the topic is about "GLUCOSE DEPRIVATION" in cancer cells.
Since you seem to be half asleep, here is an easy link that will explain to you that glucose is, indeed, carried in the hemoglobin, along with oxygen and other nutrients.
PussyCat_Eyes
1 / 5 (2) Jul 02, 2012
http://www.answer...moglobin

"The red blood cells of all individuals contain hemoglobin, which is responsible for carrying oxygen through the bloodstream. When hemoglobin combines with glucose (sugar), a molecule called glycosylated hemoglobin, or Hemoglobin A1c (HgbA1c), is formed. Since everyone has glucose in their blood, all individuals also have glycosylated hemoglobin in their blood (usually between 3 and 5 percent of blood)."
ziphead
3.7 / 5 (3) Jul 02, 2012
"
You seem to be so much smarter than actual researchers. Perhaps you are still not aware that the topic is about "GLUCOSE DEPRIVATION" in cancer cells.
Since you seem to be half asleep, here is an easy link that will explain to you that glucose is, indeed, carried in the hemoglobin, along with oxygen and other nutrients.
"

Oh come on; you got caught trying to sound more knowledgeable than you are. We have all been there.

Move on.
PussyCat_Eyes
1 / 5 (2) Jul 02, 2012
Nope. . .as a Registered Nurse, I have been trained to understand these concepts, while YOU came in here without the full awareness and with the purpose of hassling me to impress your buddy, GhostofBlotto. Then HE took your cue to call me the names he's been calling me since my 4th or 5th post on this site. I would have thought that you might be one of Blotto's sock puppets, except that you did know a small amount about blood. But not enough to give me your old putdown. YOU should be the one to move on, Troll.
TheGhostofOtto1923
4.6 / 5 (11) Jul 03, 2012
Nope. .as a Registered Nurse, I have been trained to understand these concepts
If you are an RN you are an incompetent one. You have stated that you agreed bloodletting (therapeutic phlebotomy) can be used to treat leukemia. And you think that red blood cells (erythrocites) carry glucose.
[glucose is] carried in the hemoglobin, along with oxygen and other nutrients.
With a little further research we find:

"The red blood cells of all individuals contain hemoglobin, which is responsible for carrying oxygen through the bloodstream. When hemoglobin combines with glucose (sugar), a molecule called glycosylated hemoglobin, or Hemoglobin A1c (HgbA1c)"

"[Hemoglobin A1c] is a form of HEMOGLOBIN... formed in a non-enzymatic glycation pathway by hemoglobin's exposure to PLASMA glucose."

-Hemoglobin is a chemical. It doesnt CARRY anything. The plasma carries glucose and erythrocites; and THESE carry hemoglobin, not glucose.

An RN would understand the distinction. YOU ARE NO NURSE.
PussyCat_Eyes
1 / 5 (2) Jul 03, 2012
Nope....blood letting (and you seem to enjoy repeating those words) does NOT cure leukemia. Apparently, you have again misinterpreted what Tom_Hennessy and I were talking about wrt high iron in blood. You are wayyyyy out of your league, Blotto. You need to go find Ritchie and continue your great romance with him, You won't find him with either Russkiy or me. I've read all of Russkiy's posts and the only time your Ritchie is mentioned is when YOU mention him. I assume your Ritchie is male, with a name like that.

Your attempts at being a blood expert fails. Even ziphead would tell you that. You have it all backward and upside down. Now you're saying that Hemoglobin doesn't carry anything. Go back to sleep, Blotto, and dream of Ritchie. You won't find Ritchie in a medical thread...ROFLOL
TheGhostofOtto1923
4.6 / 5 (11) Jul 03, 2012
Pussy:
Nope....blood letting (and you seem to enjoy repeating those words) does NOT cure leukemia.
-Thats 'treat' leukemia. Lets check the record...

Pussy:
There is not enough information in the article for you to determine that an oral iron chelator would be required.

Tom_Hennessy
There IS enough information. The word leukemia.
Pussy:
In leukemia where there is a preponderance of white blood cells, I would imagine that red blood cells are most important. But I'm not a doctor, so I will not comment further.
Tom:
Leukemia is not 'just' an increase in WHITE 'cells' , but , all cells. So , if one can imagine , too much iron BEFORE the increase of cells ?
Pussy:
If, as you seem to suspect, the child has a preponderance of red cells and iron, then it may be possible to do some blood-letting as in venipuncture. I don't know if they would do that because of her age and lesser volume of blood compared to an adult.
-IS WHAT YOU SAID. Right?
TheGhostofOtto1923
4.7 / 5 (12) Jul 03, 2012
Check it yourself.
http://medicalxpr...cer.html

-It appears as if Tom doesnt think you know what you are talking about either -?

If you are an RN you are an incompetent one, because you think that venipuncture can be used to treat leukemia, and that erythrocites carry glucose. And you try to lie when confronted with this. And you think that answers.com is a legitimate source for medical info.
TheGhostofOtto1923
4.6 / 5 (11) Jul 03, 2012
Your attempts at being a blood expert fails. Even ziphead would tell you that. You have it all backward and upside down.
You saying it doesnt make it so. Especially since your penchant for compulsive lying has ruined your cred.
Now you're saying that Hemoglobin doesn't carry anything.
"Hemoglobin in the blood carries oxygen from the respiratory organs (lungs or gills) to the rest of the body...collects the resultant carbon dioxide to bring it back to the respiratory organs to be dispensed from the organism...The molecule also carries the important regulatory molecule nitric oxide..."

-But nothing about glucose eh? I misspoke. Im not a professional you see. But then it is obvious that neither are you, because you think that venipuncture can be used to treat leukemia, and that erythrocites carry glucose.
PussyCat_Eyes
1 / 5 (3) Jul 04, 2012
Blotto...you''re STILL an idiot....you can't seem to remember what a person said one moment to the next. I NEVER said that venipuncture can cure or treat leukemia, YOU JACKASS. If Tom is a physician, and I don't know that...it is STILL HIS idea, not mine.
YOU HAVE A VERY BAD MEMORY, AND THAT IS SOMETHING WHICH SUFFERERS OF "DISSOCIATE IDENTITY DISORDER" HAVE A PROBLEM WITH. I SUGGEST YOU SEE YOUR PSYCHIATRIST TO FIND OUT WHY YOU REPEAT YOURSELF ALL THE TIME.
YES....GLUCOSE IS CARRIED IN THE GLYCOSYLATED GLOBULIN TO FEED THE BLOOD CELL ITSELF.
LOOK IT UP. GLUCOSE IS SUGAR. GOT THAT?

IF YOU BOTHERED TO READ THE FULL TEXT OF WHAT I SAID, YOU MIGHT HAVE NOTICED THAT I SAID, ERYTHROCYTES CARRY GLUCOSE "IN THE GLOBULIN".
YOUR READING AND COMPREHENDING WHAT YOU'VE READ LEAVES A LOT TO BE DESIRED. MAYBE YOUR BEING AN UGLY FAT PIG HAS PUT COBWEBS IN YOUR BRAIN, OR MAYBE YOU'RE ALSO HAVING A BRAIN ANEURYSM. BEST TO GET THAT LOOKED AT, YOU FAT UGLY PORKER.
PussyCat_Eyes
1 / 5 (3) Jul 04, 2012
AND YOU NEVER DID EXPLAIN TO RUSSKIY WHAT YOUR RELATIONSHIP WITH THIS RITCHY WAS THAT MAKES YOU CONSTANTLY THINK ABOUT HIM. I WOULD ALSO LIKE TO KNOW...AND MAYBE I CAN GET YOU AND RITCHIE BACK TOGETHER AGAIN. YOU SEEM TO HAVE BEEN VERY EMOTIONAL ABOUT YOUR RELATIONSHIP WITH RITCHIE. I FULLY EXPECT YOU TO TELL US ABOUT YOUR OBVIOUS ROMANCE WITH RITCHIE. I AM SURE THAT RUSSKIY STILL READS THIS WEBSITE...AND HE WOULD LIKE TO KNOW ALSO, FROM WHAT I READ IN YOUR CONVERSATION WITH HIM.
IF YOU CONFESS AS TO HOW YOU FELT ABOUT RITCHIE, MAYBE YOU ARE IN LOVE WITH HIM, I WILL DO EVERYTHING I CAN TO HELP YOU GET HIM BACK AGAIN ONCE I FIND OUT WHO HE IS AND WHY HE LEFT YOU. I'M A SUCKER FOR ROMANCE, EVEN IF YOU AND RITCHIE ARE GAY.
MAYBE YOU COULD USE A LITTLE BLOOD-LETTING?
TheGhostofOtto1923
4.7 / 5 (13) Jul 04, 2012
What an idiot. The fake nurse says:
YES....GLUCOSE IS CARRIED IN THE GLYCOSYLATED GLOBULIN TO FEED THE BLOOD CELL ITSELF.
NO it's NOT. You're so excitable when you're being stupid. Glucose is carried in the plasma to feed all the cells. But since your original ignorance was
Erythrocytes carry glucose in the hemoglobin to feed all the cells
-all your screaming cannot obscure your attempts to lie your way around your original ignorance.

And since no nurse would ever make this mistake we now have proof that the lying dimwit pussy/pirouette/ritchieguy/russkiye is no RN. Wow.
TheGhostofOtto1923
4.7 / 5 (12) Jul 04, 2012
And YOU should refrain from commenting on things of which you have no knowledge.
I understand there are people so stunted that 1) they think that they can pretend to be people they are not and 2) fail to recognize their lack when it is repeatedly explained to them by others.

You cannot pretend to be a nurse. You cannot pretend to be a Russian. You cannot pretend to be a farmer. When you try you will invariably make mistakes obvious to most anyone.

If you continue to try it means you are an imbecile. If you are by chance pretending to be an imbecile you are somewhat better at it, but it still means you are an imbecile, because no intelligent person would waste their time acting this way, and doing it as poorly as you do.

Understand?
TheGhostofOtto1923
4.6 / 5 (11) Jul 04, 2012
Dr pussy says:
I've said before and I'll say it again...there are very few absolutes in science, and most of it is still speculation. Until the real scientists can produce factual evidence to the contrary, they will remain only theory
-And you certainly cannot pretend to know science. This is a science website. Every time you pretend to know what you do not, you only embarrass yourself and make the people here uncomfortable. And invite derision.

Why try? You are wasting time and space. I am sure you must have far more rewarding things to do.
PussyCat_Eyes
1 / 5 (1) Jul 04, 2012
Blotto...you''re STILL an idiot....you can't seem to remember what a person said one moment to the next. I NEVER said that venipuncture can cure or treat leukemia, YOU JACKASS. If Tom is a physician, and I don't know that...it is STILL HIS idea, not mine.
Glycosylated hemoglobin still carries glucose, which is WHY it is called GLYCOSYLATED HEMOGLOBIN.
All your stupidity will never change that, and the research will continue to go on to deprive cancer cells of glucose, despite what you think you have found in WIKIPEDIA. I HAVE FOUND THE EXPLANATIONS IN MY TEXTBOOKS AND ON THE INTERNET AND THEY ARE THE SAME AS I'VE BEEN SAYING ALL ALONG..
YOU'RE AN IDIOT AND THAT WILL NEVER CHANGE EITHER. YOU WILL CONTINUE TO TALK TO YOURSELF IN THIS THREAD AND TELL YOUR LIES ABOUT ME AND YOU WILL STILL NOT EXPLAIN YOUR RELATIONSHIP WITH RITCHIE....AND THAT'S WHY YOU THINK I AM HE. I THINK THAT YOU ARE SEXUALLY IMPOTENT, BUT RITCHIE EXCITED YOU. HAVE FUN LOOKING FOR HIM.
OVER AND OUT.

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