Vitamin C plus antibiotic doxycycline, a lethal combination to cancer stem cells

Vitamin C plus antibiotic doxycycline, a lethal combination to cancer stem cells
Professor Michael Lisanti and his team at the University of Salford, Biomedical Research Centre have shown that cancer stem cells can be defeated by a double punch’ of an antibiotic called doxycycline in combination with vitamin C, berberine and some other off-label drugs,  supporting previous research on the anti-cancer benefits of doxycycline. Here Chris Woollams updates the research article from 2017.
 
Cancer Stem Cells regrow - if you let them
 
Cancer stem cells lie at the heart of all cancers and there is no current drug which is successful against them. Modern drugs can only ‘knock back’ tumours, reducing their size. Cancer stem cells (CSCs) always seem to remain, often with increased resistance to the drugs, free to re-grow if the right conditions are present.

In 2012, Dr. Young S. Kim of the National Cancer Institute in Bethesda showed that a poor diet would help the cancer stem cells regrow whilst a good diet containing certain bioactive natural compounds like sulphoraphanes, curcumin, piperine, Vitamin E, EGCG (from green tea), genestein, theanine and choline. Kim went on to say that all these compounds could also be obtained from quality supplements.

Go to: Bioactive compounds can stop cancer stem cell regrowth

Increasing levels of Doxycycline and then using vitamin C, to kill off cancer cells
 
Normal cancer cells are metabolically inflexible. They obtain their energy by glycolysis and need glucose - it is virtually their only fuel source. However, the core cancer stem cells at the heart of tumours are different.

 “We now know that a proportion of cancer cells escape chemotherapy and develop drug resistance; we established this new strategy to find out how they do it,”  Professor Lisanti, who designed the study, explained.

We suspected the answer lay in the fact that certain cancer cells – which we call metabolically flexible - are able to switch their fuel source. Thus, when the drug treatment reduces the availability of a particular nutrient, the flexible cancer cells can feed themselves with an alternative energy source.
 
First, the researchers added doxycycline in ever-increasing doses over a three-month period. Each time, many cancer stem cells were killed outright. Those that remained after the final treatment had become immune to the doxycycline. Interestingly, these CSCs had restricted 'feeding' flexibility and they could only use glucose in a glycolytic process. Thus they became vulnerable to a second metabolic ‘punch’.
 
Lisanti's second 'punch' - killing the damaged cancer stem cells 
 
Now the remaining cancer cells had lost their flexibility and could only use glucose - Lisanti's team took away the glucose too – by blocking the cells’ ability to use it.

There is a drug that can do this, 2-Deoxy-D-glucose, or 2-DG, but the Salford team have done a lot of work with vitamin C, and knew that to be at least 10 times more effective. When they combined it with Doxycycline it proved to be 100 times more effective. 

 
Berberine and other compounds also have strong effects
 
The researchers have identified a further eight other compounds that could be used as a “second-punch” after the antibiotic regime, one in particular was the herb berberine. Berberine has powerful effects against cancer.  It is known to attack the energy production system in the mitochondria, while also reducing blood sugar in the same way as metformin. It also kills microbes and is anti-inflammatory.
 
 
There were also a number of off-label drugs that could be repurposed to fight the cancer stem cells at this point - Chloroquin, Atovoquone and Noclosamide. We have a review on Niclosamide
 
 
“This is further evidence that Vitamin C and other non-toxic compounds may have a role to play in the fight against cancer”, according to Lisanti.
 
“Our results indicate it is a promising agent for clinical trials, and as an add-on to more conventional therapies, to prevent tumour recurrence, further disease progression and metastasis.”
 
Doxycycline and cancer
 
So, what is doxycycline?And can it fight cancer?
 
 Doxycycline is a tetracycline antibiotic, which has been used for decades. As such Doctors would regard doxycycline as a 'safe' antibiotic. None-the-less, like all antibiotics, it is known to render certain 'good' gut bacteria extinct, lost forever to the body along with their possible health benefits, and it will increase your yeast levels (and risk IBS) unless you take yeast killers such as oregano oil or caprylic acid.
 
But Doxycycline is also known to have several ‘side-effects’ useful in fighting cancer and its ability to attack cancer stem cells has been known for more than 15 years.. It also has an effect on mitochondria, the cell’s power stations.  In a 2017 study (5), doxycycline was shown to target mitochondrial biogenesis, inhibiting breast cancer development and migration, while causing apoptosis.
 
Doxycycline also inhibits enzymes called matrix metalloprotieinases (MMPs), which are involved in metastases and tissue invasion, especially in the bones. Research has shown the reduction in bone metastases in mice with breast cancer.
 
In a 2007 study (4), the use of Zoledronic acid was shown to reduce breast cancer metastases in bones by 43%. When doxycycline was added alongside the Zoledronic acid, that figure increased to 74%.
 
There was also a study from Indiana Medical School back in 1998 showing that doxycycline could inhibit prostate cancer metastases in vitro.
 
There is emerging evidence that doxycycline may work synergistically with metformin against uterine, breast and cervical cancer. There is also research on doxcycline suppressing migration, invasion and metastases of lung cancer in mice. 
 
Creative thinking on how to kill cancer stem cells
 
In the past 12 years,, 71 new cancer drugs have been launched in the UK anf the average increase in survival times is just 2.1 months according to Professor Charlie Swanton of UCL. Not only is that a poor return on the vast investment of money and brain time amongst top scientists, it also continues to ignore the truth about cancer stem cells. If you don't find something to kill them off, the cancer can always return. It should be an embarrassment to the drugs industry that in 80 years they haven't addressed this issue, but if they did, there would be no drugs industry. Fortunately, researchers like Lisanti have no vested interests.
 
Chris Woollams, former Oxford University Biochemist and founder of CANCERactive added, “I love this sort of thinking. I always remember a top British oncologist telling me that his team could ‘crack cancer’ tomorrow, if they didn’t have to waste so much time researching poorly performing drugs!
 
We have told readers about ‘Repurposing old drugs’ several times before. There are over 60 drugs created to treat other illnesses, but which have known potential benefits when used 'off-label' against cancer.
 
 
Doxycycline was one of those drugs. Lisanti and others have conducted previous research (2) that showed a number of drugs had ‘side-effects’ which would restrict Cancer Stem Cells’ metabolism, and across a number of cell lines from breast to brain cancers. They particularly emphasized doxycycline.
 
However, as a researcher myself, I do have a word or two of caution here. First, none of the research has been done in vivo with humans. In several studies it was used in very high doses in mice. I am always concerned that antibiotics screw up your microbiome. Doxycycline is no exception. And there is research (3) showing that for people with colorectal cancer (CRC), the drug can make matters worse, causing heightened gut inflammation and increasing metastases. There is also research with Myeloma, Leukemia and Lymphoma showing Doxycycline makes yeast infection and toxic load more likely. Sorry to be alarmist, but I think people with cancer should not just read a research study and rush in. The research above used increasing to very high doses of doxycycline, so you need be careful. 
 
There are other drugs that can be used off label to attack cancer stem cells - Niclosamide and Accutane (although this has strong side-effects too) are two and we have analysis of each on this Website,"
 
 
You could also read our article on how to build an 'off-label' drug protocol for your cancer, but you should always enlist proper Medical Advice. The article lists many of the drugs of interest naming the cancers for which there is research.
 
 
Dose of Doxycycline in cancer
 
This is where it becomes really confusing. Sometimes 100 mg per day is recommended, other times 300 mg. If you extrapolated some of the mice studies the dose for a 60-80 kg human would be 1200 mg! There is a lot of research on the dangers of taking antibiotics for more than 10 days.   
 
* * * * * * * * 
 
References

1. http://www.salford.ac.uk/news/articles/2017/vitamin-c-and-antibiotics-a-one-two-punch-for-knocking-out-cancer-stem-cells

2. https://www.ncbi.nlm.nih.gov/pubmed/25625193

3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4801417/

4. https://www.nature.com/articles/6603740

5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5405729/

 
 
 
 
 
 
 
 
 
2017 Research
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