NEOPLASIA 6: WARBURG EFFECT: Hallmark of CANCER. What, Why & How?
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- เผยแพร่เมื่อ 2 ต.ค. 2024
- In this short tutorial, i have described an interesting Hallmark of Cancer- WARBURG EFFECT. You will learn the What, Why and How of This Effect.
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Warburg effect in Cancer
The major metabolic shift
Reprogramming Energy Metabolism
in the presence of adequate ocygen ATP is generated by Oxidative Phosphoryation
As Oxygen Decreases Shift from Oxidative phosphorylation to Glycolysis- Anaerobic glycolysis PASTEUR EFFECT
Otto Heinrich Warburg , German Physiologist Observed that cancer cells had increased rates of glycolysis Despite the availability of adequate oxygen levels- WARBURG EFFECT
The puzzling questions
Is this phenomenon Cancer specific?
No!
This is evident in rapidly growing normal tissues too as in embryonic tissue
It is a property of growing cells but got “stuck” in cancer cells!!
Why do cancer cells activate glycolysis despite the presence of oxygen?
Assures ATP synthesis when tumor outgrows its oxygen supply
The metabolic intermediates of AEROBIC GLYCOLYSIS provides raw material for the synthesis of cellular components in these rapidly dividing tumor cells! And also favor tumor growth
Release of acid lowers extracellular pH which favors tumor invasion and suppresses immune effectors
How do they manage to activate glycolysis despite the presence of oxygen?
Induction of glycolytic enzymes BY overexpression of HIF 1
Induction of Pyruvate dehydrogenase kinase
Down regulation of mitochondrial enzymes and decrease in the number of mitochondria
Mitochondrial defects due to mutations in mitochondrial DNA leading to malfunction of oxidative phosphorylation
Significance of understanding Warburg effect
Diagnostic
This property of “glucose hunger” is used in PET scanning of solid tumors
18F-flourodeoxyglucose, a nonmetabolizable glucose derivative of glucose is used where this is preferentially taken by tumor cells/rapidly dividing cells
Therapeutic
Numerous Glycolytic inhibitors have been developed which can be potential anticancer drugs
Viewpoint!
Warburg effect is a growth promoting metabolic alteration in cancer cells
One of the Hallmarks of Cancer!
lots of explanations are given for this effect.
However the exact cause and its value,.. As of now still remains elusive!
If tumors are glucose hunger, is there any benefit to starving the body of glucose (i.e. putting the patient on a ketogenic diet or some other variation where the body uses fuel other than glucose?)
It would appear so, see The Metabolic approach to cancer, by Dr Nasha Winters, who is still surviving terminal grade 4 ovarian cancer 28 years later, TH-cam and audible.
In this case, autophagy takes place, which is triggered by low ATP. when ATP is low, the amount of AMP increases which is a used form of ATP. As the result, the ratio of AMP to ATP increases which turns on the process autophagy. cells try to use excess lipids and recycled materials from cellular compartments to produce energy.
@big Yin27 Thomas Seyfried is great to explain that. He has been treating cancer patients with great results following his protocol- ketosis , hyperbaric oxygen therapy and hyperthermia in combination
Yes, but water fasting is best
I think there's a TED talk about that yeah?
one of the best educational videos so far! Thanks!
I would be very happy with a transcript. Some parts of sentences are hard to catch
articulation mens a lot
You are better than my university professor
Your explanation was excellent, as a lay person it was very clear..Thanks..
such a concise and comprehensive explanation especially with the simplified picture. thanks!
th-cam.com/video/se0wjO4N98k/w-d-xo.html
This is very good
Very enlightening!
Thank you. You are a very good teacher. Thanks for breaking it down so it is easier to understand:)
Thanks:-) glad you like it. Please do share if you feel it benefits others too :-)
Glycolytic inhibitors? Really? Just don't eat unnecessary carbs (get your energy from animal and other quality fats, like nutrient dense organic nuts, avocado, unheated Udo's Oil, organic cold pressed extra virgin olive oil (both vacuumed sealed in fridge when stored) and minimally or non-processed organic coconut oil. Only using ghee for frying will minimize intake of toxic damaged fats. Only eat non-toxin laden, nutrient dense, low glycemic vegetables for carbs, preferably cooked if you want maximum access to the minerals, you know, like copper to support cytochrome c oxidase. Retinol loads those coppers into ceruloplasm for safe copper transport, so some animal protein will be required unless your body is really good at converting 12 beta-carotenes into retinol via a copper dependent enzyme (and you want to be sure!).
Thank you so much for explaining Warburg effect. I learned a lot from it.
Thank you for the video! It’s interesting how cancer cells are able to use HIF-1 to stop the normal aerobic respiration processes in the presence of oxygen. But how does the cancer prevent the HIF-1 from degrading under normal oxygen-rich conditions like it is supposed to do?
Dr. Thomas Seyfried improved this therapy so magnificently with great results. Keto is also very effective against many of the cancers. tumeric and Green Tea both are very powerful against cancer. ofc no sugar intake is a rule!
I am a data scientist with no background in cancer or biology. I recently joined a lab that requires one to have some basic knowledge of cancer and biology. The team members were handed over a job of explaining the hallmarks of cancer by Weinberg, and I had to give a talk on the "Reprogramming energy metabolism" part. I had no idea much less a basic understanding of it. After watching your video, I feel like I knew it a long time ago.
Knowledge can never go wasted. Your video helped A LOT.
Thank You Sir.
P.S. Also, I believe the 22 dislikes are from people who just looked at the ~13 minutes length of the video and skipped it because of that.
Saad Zaheer thanks so much. Glad you liked it 😊😊
Very well explained, thank you!
Good work
Man upload more videos , really appreciated 👌👌👌👌
brilliant! I like your way of explaining.
Glad you liked it!
*SO WUT are the BAD FOODS???*
*WUT are the GOOD FOODS??*
interestingly, lactate is certainly not a metabolic "end-point" as taught in many medical schools, but is instead a potent signalling molecule and is often used as a source of energy itself. Lactate (lactic acid in solution) can also be transported to the liver and used in gluconeogenesis. Cancer cells can use numerous other biomolecules such as glutamine and under the new discovery of the "reverse Warburg effect", can manipulate cells of the stroma to package and deliver all the metabolic starting molecules they need
Superb videos sir ,can u please make videos on other topics as well
th-cam.com/video/se0wjO4N98k/w-d-xo.html
Make a video on invasion and metastasis(neoplasm chapter) in 2 to 3 days.. Plzzzzzzzzzz.. I need it
Not just like sir we love the video.. I just wonder how underrated these videos r... Thanks a lot for these treasures and pls keep uploading more so that many can benefit from ur knowledge and understnding and clear crisp concepts and soothing explanations
thank you sir
The best explanation ever. Who is the author of this wonderful class? Thank you!
Amazing!❤️
best tutorial on cell meatbolism and warburg effect i ve watched so far.Thank you sir for contributing to our education.
thankss so much :-)
super helpful thank you!!
It was so helpful with such a detailed and toned answers for all questions. Thanks you so much! Keep doing more of pathology videos!❣
Very useful, sir. It'll be more helpful if you give your references in the end.
i am an oncologist and never really understood why the hell are some antigens which are expressed during the embryogenesis expressed during the processs of malignancy (a.k.a oncofetal antigens -tetsis antigens ny-eso).
today i had an epiphany kind of efffect after hearing your video .
careful. The warburg effect is seen in many other types of cell proliferations too. I had the same epiphany as you several years ago. There is some interesting research into oncofetoproteins though and it's hard to say if these proteins are being expressed coincidently, are acting as tumor suppressors, or are acting as oncogenes, or something else. Alpha-fetoprotein is reexpressed in most liver cancers (most of which are caused by EBV), but some new research has shown it has some interesting antiviral properties. Even the pregnancy associated protein HCG is often expressed as well. I believe the reexpression of fetal genes is a window into something of great importance, even the hox genes are repeatedly being seen expressed in human cancer. Perhaps it is not individual genes from fetal genesis that are being expressed, but gene programs...
Sir you were amazing and the tutorial was very enriching. learnt so many things..thank you.
Thank you so much.....
very useful, thank you!
Great explanation ..easy to understand thank you
Wouldn't a lack of bioavailable copper dependent cytochrome c oxidase in complex 4 explain the transformation of a normal cell to a cancer cell? The oxygen needs cytochrome c oxidase to convert it into water and ADP, but that conversion can't be done without cytochrome c oxidase, can it? If it doesn't get done, the cancer mechanism you describe all fall into place. Assuming copper is in the conventional food supply when it hasn't been added to fertilizer for probably 80 years isn't a valid assumption, is it? Also, retinol is required to load copper into ceruloplasmin so that the copper can safely flow throughout the body, but that was removed from the Western diet when it was declared animal fats are bad, right?
BTW, I heard about this concept from Morley Robbins, a former hospital executive and consultant who "retired" to become an scientific literature autodidact who spends about 15-20 hours a week reviewing the actual source data in the scientific literature, as well as calling up the authors and discussing their conclusions. He's been doing this for about a decade now.
Yes sir !, such a really good explanation and data recopilation !. It'll be awesome if you can also post the articules or your references, thank you so much. one more suscriptor.
What happens if you eat food containing cancer cells or tumor?
Very nicely explained, especially the mechanism behind this reprogramming of metabolism
This helped a lot. Thank you sir!
Wouldnt this create Ketoacidosis? So intentionally creating a state of Ketosis perhaps create a cancerous environment is this to say that a diabetic inability to convert glucose might make for perfect conditions for cancer of all types? Someone please let me know I have been searching and studying on this subject for so long...ive come back to basics to see where it is...the missing link...what is it to know...what is it to understand this formula for reaching a solution to creating homeostasis in an already infected body and also halting blocking the development of regeneration of those cancerous cells as well as preventing any cancer cells to develop completely. I was thinking the entire dna structure for predisposition might be successfully reinvented by the frequency by capacitors over a certain amount of time might be studied and or the removal of an individuals dna structure mechanically altered then somehow reintroduced to that same individuals body even by using a component of a cancer cells voracious appetite for glucose over a short period until the dna structure itself has been completely rid of old dna structure.
Beautifully done sir🙏🏽👌👌🏼
oh no at 7:00 I could not understand what was said and there is no transcript.
otherwise very good information.
Please make a vedio on feroptosis
is this named for the super "elite" german banking family warburg?
I bow to ur explanation..thank you so much..for making a smooth understanding
I really didn't need this talks to fast can't understand but then I learned sometime ago about cancer and fermentation CC WOULD BE NICE BUT THEN I WOULD HAVE TO STOP AND START TO MUCH. I am glad for those below I am not a speed listener
I looveee ur videos...u put so much effort in collecting material,summarizing it,making slides....i hope other students may also get benefit from these lectures
Thank you 😊
Please do share 😊
A very understandable explanation. Thank you.
Amazing 🎉❤🎉
DR. OTTO WARBURG WAS A TWO-TIME NOBEL PRIZE WINNER. 😎 🌹🌹🌹🌹🌹🌹👏👏👏👏👏👏👏👏👏👏👏
now I have ACTUALLY started loving pathology ;)
Do all types of cancer cell demand GLUCOSE? i.e. Benign and malignant cells require GLUCOSE as the same amount ?
I wish you didnt have such a heavy accent. Its so difficult to instance what you're saying....
Rewind, play, rewind play, still cant understand. :/
so clearly explained.
thanks.
if you are going to upload more such videos about topics where students get confused, I am ready to subscribe.
otherwise, since I liked the video I have "liked" it.
but assure me and others reading this post about possibilities of future videos to get more subscriptions.
thanks again for such clear illustration.
Cancer cells do produce much less ATPs and therefore much less energy. All the energy produced in a normal cell is not entirely used up. Some percentage of it is converted into heat. This heat is essential for sustaining normal functioning of the cell. Cancer cells are heat starved and this factor promotes their growth and proliferation. In other words, they maintain low heat profile which results in total disorganisation within the cell. This theory is supported by the fact that they do not produce conversion heat when exposed to high energy radiation.
Wonderful! ;)
man you are really good. you first explain all background knowledge then coming to the main point. you can do more videos on 2nd year MBBS PATHOLOGY
If its generating energy without oxygen ,he should call it as anarobic glycolysis right, y did he call it as aerobic glycolysis?
Excellent video sir,crisp and made my concept crystal clear😊
Thank you for the video. But why is 2-aminomuconic acid on the cover?
Sir great video, I came to know that cancer cells also use amino acids like glutamine for survival not only glucose ! Please reply me sir , thank you
Glutamine and alanine are substrate for gluconeogenesis. The cell converts them into glucose.
Thank you so much sir easily understandable 😊
You saved my life and explained this really well! We should get you to lecture at my medical school!
Could you do a video on prostate cancer? Thanks. here is some info I found...
Prostate cancer starts with OXPHOS not glycolysis or Warburg effect :
Metformin is an OXPHOS Inhibitors 🙂
Seems like Glycolysis or Warburg effect starts with epithelial-mesenchymal transition (EMT) when the cancer starts to move.
..."(Fig. 1). However, during carcinogenesis, ZIP1 levels decrease and OXPHOS is promoted.8 Nevertheless, this only occurs during the first steps of carcinogenesis. One study shows that the mitochon-drial content does not change during carcinogenesis, but OXPHOS decreases with invasiveness. 22..."
"The prostate is metabolically unique since the differentiated tissue is glycolytic instead ofoxidative. Prostate cancer (PCa) transformation involves ametabolic switch to oxidative phosphorylation (OXPHOS),which later, in the advanced castration-resistant prostate can-cer (CRPC) phenotype, turns again to glycolytic"
"WNT/b-catenin and theinsulin-like growth factor (IGF) 1 pathways seem to play amajor role in the most aggressive phenotype of CRPC.18"
"PCa cells use interleukin-6 secretion toactivate glycolysis in cancer-associated fibroblasts, which inturn, increase lactate secretion.25Lactate is consumed byOXPHOS-dependent PCa cells, having a role in redoxhomeostasis and angiogenesis.26"
"GLUT1is related to recurrence after radical prostatectomy.62"
"fructose uptake might have a rolein PCa progression, particularly, at early stages."
onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ijc.31165?fbclid=IwAR1eFkozn7LV8yOBd1L_kAmgq32NR23nIV5R7AG8qRETjasJahQPb7GnKDg
Excellent
Very interesting
A great video. Thank you.
absolutely good one! cleared all doubts! thank you.
Your cancer videos are amazing, thanks so much!
ı have questioned if it is using glucose to lactate why we are saying it is aerobic, it is anaerobic, isn't it. and thank you for your good presentation
Hello sir, can you kindly help me to know about "pentalenolactone inhibits glycolysis by inhibiting specifically glyceraldehyde-3-phosphate dehydrogenase" how?? and how its resistant towards glyceraldehyde-3-phosphate dehydrogenase?
Pentalenolactone has an epoxi lactone,this epoxi group has an towords resistant bacterial cell wall formation.can i get the answer ,i am looking for it?
Extremely helpful. Thanks to you, I guess I won't be tanking my cancer biology exam.
Plz make video on disease of infancy and childhood
Greate information , we can consider anaerobic respiration reaction sulphor based and role of methyl donors
Thank you bruh ! Thats so informative
th-cam.com/video/se0wjO4N98k/w-d-xo.html
Such a beautiful video, we don't need to read the text after such a beautiful explanation. Please Sir, keep posting videos on important theory questions and practicals including slides which would be of greatl help for us PG students.
Keep uploading more vedios
👍
Thanks for your all videos.Can u add subtitles pls.
Best explanation I came across. Thank you very much.
Cause is the damage to respiration, due to damaged mitochondria
Sir,great explanation. I was struggling to understand the concept qnd now it is much clear. Thank you very much.
First thank you for the great video, Can you tell me what is the reference?
Nice vedio
Tq sir for such good explanation
Can u put more topics related to systemic pathology
Good Video, nice explanation of possible causes for the Warburg Effect, in general. Cheers!
Beautifuly explained. Thanks
You should have some one who proficient in english rerecord this for you.
You should be more international
Interesting information! Thank you for this video Sir.
Sir why don't you upload more videos?
please, someone, help in 6:09 what did he just say??
"that is because the activation of what????" I didn't understand
Tht is bcz of activation of oncogenes& loss of tumour suppressor genes......
Seriously loved this.
th-cam.com/video/se0wjO4N98k/w-d-xo.html
what sources did you take this information from? thanks for the video!!
Donde puedo conseguir este libro ?
Such a great video!Thank you!
Fantastic 😊
Awesome explanation ❣️
Excellent presentation. Thanks