Killing cancer cells by targeting glucose metabolism

Cristina Muñoz Pinedo. Cell Death Regulation Group IDIBELL (Institut d'Investigació Biomèdica de Bellvitge)
Oncogenic transformation promotes metabolic changes which makes tumors "addicted" to certain metabolites. For this reason, inhibition of tumor metabolism is a promising new therapeutic approach. However, little is known about how metabolic stress triggers tumor cell death.
Glucose depletion has been shown to kill cells either by necrosis (non-apoptotic, pro-inflamatory cell death) or by the mitochondrial pathway of apoptosis. Our studies indicate that several tumor cell lines of different origins die in a non-apoptotic manner when deprived of glucose. However, we have recently described an atypical apoptotic pathway engaged in cells from solid tumors. Surprisingly, apoptosis induced by glucose deprivation is independent of the Bcl-2-regulated mitochondrial pathway. We will describe this apoptotic pathway mediated by caspase-8, which is the initiator caspase engaged by death receptors of the TNF family.
2-deoxyglucose is a non-metabolizable glucose analog which competes with glucose and has shown anti-tumor effects in animals.
Moreover, this compound is been tested in clinical trials. We are currently studying sensitivity of tumor cells, especially sarcoma cell lines, to 2-deoxyglucose. Interestingly, 2-deoxyglucose promoted apoptosis in cell lines in which glucose deprivation promoted necrosis, suggesting different death mechanisms. 2-deoxyglucose activates the mitochondrial apoptotic pathway and regulates several apoptotic proteins in p53-deficient cells. We found death under normoxia to be associated to endoplasmic reticulum stress rather than lack of ATP. We will discuss the signaling pathways involved in responses to nutritional stress and how to improve sensitivity of tumor cells to metabolic targeting.

[@judexacosta686]

Thank you very timely

[@TheRichSolution]

Thanks for putting this out there about cancer and metabolism.

[@JJAngleton]

Very good explanation! Thanks

[@irenetan3620]

Hi, can you please give us links to your articles presented in this lecture? Thanks

[@Shawn022]

GREAT VIDEO .....Thanks for Posting :O)

[@Beejgrpa]

Like a petrol fire, you can try and stop electrical spark, heat & compression, naked flame or whatever else from causing combustion, but removing the petrol from the equation is a far more effective solution, and if not the ultimate or final, shouldn't the initial solution be the one that has the greatest positive effect?

[@andrereog5419]

Has a cure been found?

[@andrereog5419]

Have you a simple advice?

[@salman125]

This is a very interesting video, but I needed to clarify few things in simple terms. I wish Cristina can reply in simple language (for non-technical people) like myself. I ask this because I am myself a cancer survivor trying to keep it coming back again. If I fast twice a week (no food or water from dawn to dusk), how this near starvation shock and reduced glucose level in my body will affect normal and cancer cells?

[@NO1xANIMExFAN]

If your fasts are from dawn to dusk, then doing so twice a week wouldn't affect normal cells nor cancer cells. Glycogen in the liver depletes after approximately 3 days, which means that any fast that is shorter than that doesn't actually starve the cancer cells.

[@ludwigrotin5891]

2 days, near starvation? You gotta be kidding me. You can fast up to 40 days, but you have to drink water. The body doesn't enter starvation mode until 40 days after fasting. Read this book, the atomic power of prayer and fasting. It's a faith book by Franklin hall and he's an expert on fasting.

[@robertgrayraleigh]

I suggest u speak much more slowly so that people with different accents have time to keep up with your words

[@agazaman]

to much estrogen this gurl....but cute presentator