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Conferences DCA Research Topic #83
Reading Topic #83, reply 20
davidportia
Member since Jul-23-08
61 posts		 Feb-16-09, 07:04 AM (PST)
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20. "RE: DCA and the MAAI pathway"
In response to message #12
 
   >Interference with the tyrosine degradation pathway may be
>just one way that dca can lose its effect and the cause may
>be quite subtle. For instance if not broken down, the
>tyrosine catabolite succinylacetone inhibits aminolevulinic
>acid dehydratase, which increases delta aminolevlinic acid
>(also known as 5-ALA) which induces iron release from
>ferritin via free radical production. High levels of iron
>are drivers of tumour growth and oxidative damage.
>
>Most of us are aware that mainstream chemo also loses
>effectiveness and in some cases drives metastasis by
>upregulating the NF-KB pathway (which can hopefully be
>inhibited by taking alpha lipoic acid/curcumin. And of
>course individual responses may reflect subtles differences
>in our genes, ages, the food we eat. The amount we take...
>
>So hard to know what to do, there is so much trial and
>error. But a first step should be to ask any long term good
>responders exactly what they are on in terms of as complete
>list of pharmaceuticals, supplements (incl brands), diet,
>their age, type of cancer if known. Something they are
>taking may be acting in concert to make dca more effective
>or it may be preventing a downstream pathway that ultimately
>leads to resistance in some people. Include the time of day
>drugs/supplements are taken.
>
>If we compare the long terms responders to the resistant or
>non-responders something might just stand out. Also include
>side effects if any. For instance aminolevulinic acid
>accumulation might mimic the symptoms of Acute Intermittent
>Prophyria - constipation, abdominal pain, vomiting,
>hypertension, PN, seizures, delirium, coma, depression and
>it may give us the clue that dca has exhausted the MAAI/GSTZ
>pathway in these persons resulting in apoptosis inhibition
>via tyrosinemia triggered chronic stress via Akt, BAD & Bcl.
>
>For dca to work there also needs to be an intact
>mitochondrian apoptopic pathway. One of the earlier
>discussion I had here was considering the use of acetyl l
>carnitine to boost cellular cardiolipin levels and also
>taking high dose DHA to load up the cardiolipin so that when
>dca restarts the mitochondria the free radicals generated
>within the cell by both energy pathways triggers apoptosis.
>The older you get the lower your cellular cardiolipin
>levels. If you also have diabetes you will have lower
>cardiolipin levels through a hypothesized upregulation of a
>cardiolipin digesting enzyme. But we don't have any data on
>whether this will work for cancer, although ALC has been
>trialled separately in chemo patients to reduce neuropathy.
>
>Could you give us more data on your father? Please be aware
>I don't have any medical training but I hope we can make a
>difference and figure out why he stopped responding which
>would help us all. For example if he was on statins for
>chloresterol which can be cancer protective because of their
>anti inflammatory effects they also prevent production of
>coenzyme q10 a required co-enzyme for cellular energy
>production and which in breast cancer patients at least, has
>been shown to be at lower levels.
>
>I'm assuming he was on alpha lipoic acid? Originally I was
>against its use as a potent anti-oxidant as I thought it
>would prevent ROS mediated apoptosis in the cell but Sandra
>has changed my mind and the studies seem to support its
>action as an anti cancer agent. Curcumin also has good NF-KB
>and apoptosis inducing effects. However it may have trouble
>being absorbed into the body.
>
>http://www.febsletters.org/article/S0014-5793(08)00339-6/abstract
>Abstract
>We report here that alpha-lipoic acid (α-LA), a
>naturally-occurring antioxidant, scavenges reactive oxygen
>species (ROS) followed by an increase in apoptosis of human
>hepatoma cells. Apoptosis induced by α-LA was dependent
>upon the activation of the caspase cascade and the
>mitochondrial death pathway. α-LA induced increases in
>caspase-9 and caspase-3 but had no significant effect on
>caspase-8 activity. Apoptosis induced by α-LA was found
>to be mediated through the tensin homologue deleted on
>chromosome 10 (PTEN)/Akt pathway. Prior to cell apoptosis,
>PTEN was activated and its downstream target Akt was
>inhibited. Our findings indicate that increasing ROS
>scavenging could be a therapeutic strategy to treat cancer.
>
>Also see this on chloroquine. Unfortunately the dose of its
>less effective counterpart quinine from Tonic Water probably
>wouldn't be effective (although if it doesn't hurt...)
>
>http://www.ncbi.nlm.nih.gov/pubmed/19194831?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
>
>The present study was to investigate the anticancer effect
>of chloroquine on proliferation of mouse colon cancer cell
>line CT26 in vivo and in vitro and the possible mechanism.
>We found that chloroquine inhibited CT26 proliferation by
>concentration- and time-dependent manner. This effect was
>associated with apoptosis induction and decreased level of
>phosphorylated p42/44 mitogen-activated protein kinase and
>phosphorylated Akt. The in vivo study showed
>chloroquine-reduced tumor volume and prolonged survival time
>in CT26-bearing mice. These observations indicated
>chloroquine could inhibit CT26 proliferation by inducing
>apoptosis both in vitro and in vivo, providing its
>chemotherapeutic potential of human cancers.
>
>Mack

Dear Mack,
The first round (45 days) my dad was taking very minimum supplements, because I was not able to get everything for him at the time. The result was so good, that I hardly believe it is true. For the second round ( 2 months) I did got many supplements, like flaxseed oil, Lecithin, alpha Lipoid acid, Potassium, Magnesium, etc, but the result was very negative, so I suspected that something in this round may have worked up to stop the effectiveness of DCA to cause this. So I ask him to go back to what he took during the first round. But the result of the third round (exactly as the first round) is alarmingly worse, which convinced me that DCA has stopped working for him. He has been always taking DCA, without on and off schedule like others did. I realize that this could be one of the reasons why DCA stopped working for him. FYI, he never exceeded the dosage of 26mg/kg/day during his entire usage of DCA.
I am thinking to add artesimin/artesunate, because it can combine with free iron and this may work in synergy with DCA, but until today, I still can not find them now for my dad.
Best regards,
David


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 DCA and the MAAI pathway [View All], Mack, 06:01 AM, Feb-05-09, (0)  

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