Rb What Do You Make Of This--oleate Helps Survival Of Bc Cell Lines Even Wout Serum!

[Lani]

Biochem Cell Biol. 2007 Jun;85(3):301-10.
Upregulation of cellular triacylglycerol - free fatty acid cycling by oleate is associated with long-term serum-free survival of human breast cancer cells.

Przybytkowski E, Joly E, Nolan CJ, Hardy S, Francoeur AM, Langelier Y, Prentki M.
Molecular Nutrition Unit, Montreal Diabetes Research Center, Centre de Recherche du Centre Hospitalier de l'Université de Montréal and Institut du Cancer de Montréal, Montréal, QC, Canada.
We previously showed that exogenous oleate protects human breast cancer cells against palmitate-induced apoptosis in part by increasing esterification of this free fatty acid (FFA) into triacylglycerol (TG). Here, we studied the mechanism whereby oleate protects these cells against apoptosis induced by serum withdrawal. The metabolism of FFA, TG, and glucose, in parallel with long-term cell survival in the absence of serum, was investigated in a panel of human breast cancer cell lines and in nontransformed MCF-10A cells after treatment with exogenous oleate. Short-term (3-24 h) exposure of MDA-MB-231 human breast cancer cells to exogenous oleate resulted in a dose-dependent long-term (10 day) serum-free survival that correlated with the accumulation of TG in lipid droplets and with upregulation of lipolysis. Both effects persisted for several days after oleate removal. Rapid TG lipolysis and FFA re-esterification, supported by high rates of glycolysis that provide the glycerol backbone for TG synthesis, are consistent with the presence of very active TG-FFA cycling in human breast cancer cells. Only the cancer cell lines capable of accumulating TG showed long-term serum-free survival after oleate treatment. The results suggest that upregulation of TG-FFA cycling induced by oleate may be involved in maintenance of human breast cancer cell survival.
PMID: 17612624 [PubMed - in process]

[R.B.]

Thank you for that Lani.

Olive oil seems to work against cancer by different mechanisms by virtue of both the fats and other ingredients e.g.

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=PubMed&Cmd=ShowDetailView&TermToSearch=17490486&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVDocSum

I will give it some thought. I will see if the full trial is free to view. It would have been interesting to see a comparison with other free fatty acids eg DHA, AA, EPA, LA etc.

I was also not aware palmitate killed cancer cells.

Was the oleate in the presence of the palmitate.

Are the cells proliferating or growing or are the fats being used for fuels.

Do these cells normally have an ability to store fats as part of their usual activities as breast cells - milk creation which must include fat manufacture accumulation and storage?

I will have look at the previous oleate / other fats' trials if I get time to see if my understanding is up to any intelligent comment.

RB

[RobinP]

I wonder if these in vitro studies were on just bc cell lines that were only er sensitive ones, as there is a lot of evidence from Dr Menendez that oleic acid has efficacy in her2 bc.

[R.B.]

Robin,


From memory I think the MDA cell line is an HER 2 line, but I am not certain.

And yes Dr Martinez is pretty definitive in a few trials. He also suggests ensuring adequate supplies of threes and nines.

Fats work in so many different ways, and impact the cell metabolism from a number of angles, and it is so complex I think it is difficult to reach any more thoughts without access to the trial, which is a pay for view only.

We are also looking at it out of context of the body and real world in the sense that it may work by displacing something else like say linoleic acid (omega six), and we don't know if that figured here.

At a basic level I think it comes back to supplying the body with the raw materials it has grown up with, taking into account that most people will have omega six stores that will take a while to shift, and many have blocked fat conversion pathways to make DHA etc.

E.g. more three than six and some long chain threes, keeping an eye out for long chain omega six deficiency in a few. The point being for most our modern diets do not supply us with what we need by a long way.

I do have some questions and thoughts on the above but they are too hazy to post.

Please all discuss dietary change with your doctor. This is information and not advice.

RB

[RobinP]

MDA line may lack estrogen; however, it may also lack her2. Perhaps thats why it didn't respond oleic acid. I also think the in vivo impact may differ than the in vitro... we certainly lack human studies when it comes to the cancer diet. Like I said before, the impact of particular fatty acids is much more defined for the cardiac diet.

[Christine MH-UK]

Just did a quick check through pubmed. Clearest example: "Medium dose-effect analysis indicates that OSU-03012 potentiated trastuzumab's antiproliferative effect in HER2-positive cells, especially in SKBR3/IGF-IR cells, through the down-regulation of PDK-1/Akt signaling. This synergy, however, was not observed in HER2-negative MDA-MB-231 cells."

[R.B.]

Thanks Christine for taking the trouble to post this.

I just wondered if there might be other strains of MDA-MB-231 as well.

Also in the cycle of breaking and remaking referred to "Rapid TG lipolysis and FFA re-esterification" what fats are being made. Are the cells making the long chain omega nines??.

RB