Re: Dichloroaectate acid DCA and Cancer Cells

On Fri, 02 Mar 2007 04:35:06 GMT, "Sledgedog"
<global.computer@xxxxxxxxxxx> wrote:

What are people's experiences with this new hope?

Not saying it works NOT saying it doesn't
Clinical trials are needed

what say ye all?

It's been just over a month since the news about the potential
anti-cancer effects of DCA started to circulate, so it's IMHO highly
unlikely that anyone could have anything worthwile to report about the
possible effects. Although the potential responses could be observed
fairly quickly, to detect the lasting long-term effects requires
yaears of follow-up.

Yes, clinical trials are required. I hope that financing for them can
be arranged although this is an old drug, whos patent has expired.

While we wait for experiences and clinical trials, let's see again
what we know now:

Cancer cells make their energy throughout the main body of the cell,
rather than in the mitochondria. This process, glycolysis, is
inefficient and uses up vast amounts of sugar. Until now it had been
assumed that cancer cells used glycolysis because their mitochondria
were irreparably damaged. However, Dr. Evangelos Michelakis of the
University of Alberta in Edmonton, Canada, and his colleagues
tested Dichloroacetic acid (DCA) on human lung, breast, brain cancer
cells and healthy cells cultured outside the body, and found that DCA
reawakened the mitochondria in cancer cells. The cancer cells then
withered and died. The healthy cells were unaffected. Tumours in rats
deliberately infected with human cancer also shrank drastically when
they were fed DCA-laced water for several weeks.

The study is

Bonnet S, Archer SL, Allalunis-Turner J, Haromy A, Beaulieu C,
Thompson R, Lee CT, Lopaschuk GD, Puttagunta L, Bonnet S, Harry G,
Hashimoto K, Porter CJ, Andrade MA, Thebaud B, Michelakis ED.
A mitochondria-k(+) channel axis is suppressed in cancer and its
normalization promotes apoptosis and inhibits cancer growth.
Cancer Cell. 2007 Jan;11(1):37-51.
PMID: 17222789 [PubMed - in process]
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17222789>
<http://www.cancercell.org/content/article/abstract?uid=PIIS1535610806003722>

University of Alberta news releases:

Small molecule offers big hope against cancer
University of Alberta, News release January 16, 2007
<http://www.expressnews.ualberta.ca/article.cfm?id=8153>

Small molecule offers big hope against cancer- Information and Videos
Videos of Dr.Michelakis' interview.
University of Alberta, Faculty of Medicine & Dentistry, News release
January 17, 2007
<http://www.med.ualberta.ca/news-publications/article.cfm?id=123>


News articles:

The Why Files: Small molecule could be a big cancer fighter
<http://whyfiles.org/shorties/225cancer_drug/>

Cheap, safe drug kills most cancers
New Scientist, 17 January 2007
<http://www.newscientist.com/article/dn10971-cheap-safe-drug-kills-most-cancers.html>

Editorial: No patent? No cancer drug development
New Scientist, 20 January 2007
<http://www.newscientist.com/channel/opinion/mg19325873.000-editorial-no-patent-no-cancer-drug-development.html>

Small Molecule Offers Big Hope Against Cancer
Medical News Today, 19 January 2007
<http://www.medicalnewstoday.com/medicalnews.php?newsid=60958>

Small Molecule Offers Big Hope Against Cancer
ScienceDaily, January 17, 2007
<http://www.sciencedaily.com/releases/2007/01/070116134001.htm>

Cramping tumours
The Economist, Jan 18th 2007
<http://www.economist.com/science/displaystory.cfm?story_id=8548706>

Small molecule offers big hope against cancer
physorg.com, January 16, 2007
<http://www.physorg.com/news88194392.html>


Wikipedia's article about Dichloroacetic acid:

<http://en.wikipedia.org/wiki/Dichloroacetic_acid>


Searching Medline for Dichloroacetate OR "Dichloroacetic acid" returns
1056 studies at the present time:

<http://tinyurl.com/358cpr>


Here's a couple of recent studies about the use of oral
dichloroacetate (DCA) in the treatment of children with congenital
lactic acidosis caused by mutations in the pyruvate dehydrogenase
complex (PDC):

Berendzen K, Theriaque DW, Shuster J, Stacpoole PW.
Therapeutic potential of dichloroacetate for pyruvate dehydrogenase
complex deficiency.
Mitochondrion. 2006 Jun;6(3):126-35. Epub 2006 May 3.
PMID: 16725381 [PubMed - indexed for MEDLINE]
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?itool=abstractplus&db=pubmed&cmd=Retrieve&dopt=abstractplus&list_uids=16725381>

Stacpoole PW, Kerr DS, Barnes C, Bunch ST, Carney PR, Fennell EM,
Felitsyn NM, Gilmore RL, Greer M, Henderson GN, Hutson AD, Neiberger
RE, O'Brien RG, Perkins LA, Quisling RG, Shroads AL, Shuster JJ,
Silverstein JH, Theriaque DW, Valenstein E.
Controlled clinical trial of dichloroacetate for treatment of
congenital lactic acidosis in children.
Pediatrics. 2006 May;117(5):1519-31.
PMID: 16651305 [PubMed - indexed for MEDLINE]
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16651305>


DCA prevents and reverses pulmonary hypertension:

McMurtry MS, Bonnet S, Wu X, Dyck JR, Haromy A, Hashimoto K,
Michelakis ED.
Dichloroacetate prevents and reverses pulmonary hypertension by
inducing pulmonary artery smooth muscle cell apoptosis.
Circ Res. 2004 Oct 15;95(8):830-40. Epub 2004 Sep 16.
PMID: 15375007 [PubMed - indexed for MEDLINE]
<http://circres.ahajournals.org/cgi/content/full/95/8/830>

Michelakis ED, McMurtry MS, Wu XC, Dyck JR, Moudgil R, Hopkins TA,
Lopaschuk GD, Puttagunta L, Waite R, Archer SL.
Dichloroacetate, a metabolic modulator, prevents and reverses chronic
hypoxic pulmonary hypertension in rats: role of increased expression
and activity of voltage-gated potassium channels.
Circulation. 2002 Jan 15;105(2):244-50.
PMID: 11790708 [PubMed - indexed for MEDLINE]
<http://circ.ahajournals.org/cgi/content/full/105/2/244>


DCA also has antidiabetic effects in the type 2 diabetes:

Stacpoole PW, Greene YJ.
Dichloroacetate.
Diabetes Care. 1992 Jun;15(6):785-91. Review.
PMID: 1600837 [PubMed - indexed for MEDLINE]
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=1600837>

Peer G, Graf H.
[Sodium dichloroacetate--a substance with manifold therapeutic
potential]
Wien Klin Wochenschr. 1990 Feb 2;102(3):65-9. Review. German.
PMID: 2180210 [PubMed - indexed for MEDLINE]
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=2180210>

Stacpoole PW.
The pharmacology of dichloroacetate.
Metabolism. 1989 Nov;38(11):1124-44. Review.
PMID: 2554095 [PubMed - indexed for MEDLINE]
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=2554095>

Park R, Radosevich PR, Leach WJ, Seto P, Arieff AI.
Metabolic effects of dichloroacetate in diabetic dogs.
Am J Physiol. 1983 Jul;245(1):E94-101.
PMID: 6869532 [PubMed - indexed for MEDLINE]
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=6869532>
<http://ajpendo.physiology.org/cgi/content/abstract/245/1/E94>


Other interesting DCA studies:

Andreassen OA, Ferrante RJ, Huang HM, Dedeoglu A, Park L, Ferrante KL,
Kwon J, Borchelt DR, Ross CA, Gibson GE, Beal MF.
Dichloroacetate exerts therapeutic effects in transgenic mouse models
of Huntington's disease.
Ann Neurol. 2001 Jul;50(1):112-7.
PMID: 11456300 [PubMed - indexed for MEDLINE]
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=11456300>

Oishi K, Yoshioka M, Ozawa R, Yamamoto T, Oya Y, Ogawa M, Kawai M.
[Dichloroacetate treatment for adult patients with mitochondrial
disease]
Rinsho Shinkeigaku. 2003 Apr;43(4):154-61. Japanese.
PMID: 12892050 [PubMed - indexed for MEDLINE]
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=12892050>


Adverse effects:

DCA can cause reversible peripheral neuropathy due to its
demyelinating effect:

Felitsyn N, Stacpoole PW, Notterpek L.
Dichloroacetate causes reversible demyelination in vitro: potential
mechanism for its neuropathic effect.
J Neurochem. 2007 Jan;100(2):429-36.
PMID: 17241159 [PubMed - in process]
<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17241159>



--
Matti Narkia
.

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