Cancer and ketones

Just a brief post:

Dr Fine is looking at metabolic management of cancers. Cancers express uncoupling protein 2 (UCP2). UCP2 plugs in to the mitochondrial inner membrane, allows protons through, lowers the voltage across the membrane and so reduces both ATP and free radical production by the mitochondria. It might not be as physiological as UCP3, more of a survival tactic in hyper energetic states. UCP2 is not commonly present in normal tissues.

Lack of respiration drives the use of glucose-lactate fermentation, adapted to the the hypoxic environment which is a common location of cancer cells.

Ketone bodies are very special as regards mitochondria. I'll post on this eventually. But they switch on respiration (mitochondrial O2 based ATP production) and switch off glycolysis, ie they cause insulin resistance, but not at the GLUT4 level (post here). Dr Fine points out that cancer cells tend to use GLUT1, not GLUT4, so a non GLUT4 method of glucose deprivation might be a good idea. If a cancer cell's mitochondrial inner membranes are punched full of holes (UCP2s) then ketones cannot generate mitochondrial ATP effectively, but can still inhibit glycolysis. Result: decreased ATP and decreased cell growth. This is an aggressive cancer on a ketogenic diet.

There is no suggestion of apoptosis of the cancer cells, this requires increased free radical production. But slowed cell growth is a better option than runaway growth if you want your immune system to stand a chance of saving your life....

Dr Fine discusses the "model" like nature of his model, and it's flaws, nicely. Just tissue culture at the moment, but the project is aiming to go clinical at some stage soon.

OK, time for a nap before a night shift.

Peter