Antibiotics and vitamin C could kill cancer cells

"Vitamin C and antibiotics could be up to 100 times more effective than drugs at killing cancer cells – without the side effects," reports the Mail Online. The news comes from the results of a study that found a new two-pronged approach using the antibiotic doxycycline followed by vitamin C could kill cancer cells.

Doxycycline killed many cancer cells, but others became resistant. The resistant cells were then destroyed by vitamin C.

While this is encouraging news, it needs to be put into context. The experiments all took place in the laboratory. Researchers used human breast cancer stem cells, but didn't perform any studies on animals or humans.

This means we don't know how successful this strategy could be – and the Mail's claim there would be no side effects is unsupported.

Though both doxycycline and vitamin C are safe to use in humans, more research is needed to find out how they interact with other cancer treatments and therapies before this can be recommended as a new approach to treating cancer.

Where did the story come from?

The study was carried out by researchers from the University of Calabria in Italy, and the University of Manchester and the University of Salford in the UK.

It was funded by both UK universities, the Healthy Life Foundation, the Associazione Italiana per la Ricerca sul Cancro (AIRC), the European Union, and various private donations.

The study was published in the peer-reviewed journal Oncotarget on an open access basis, so it's free to read online.

The Mail reported on the study reasonably accurately, but didn't point out clinical trials are needed to see if the approach would be effective – and safe – in humans.

What kind of research was this?

This research involved a series of laboratory experiments performed on human cancer stem cells.

Although both doxycycline and vitamin C are safe to use in humans, we don't know whether the dose and combination required to kill cancer cells would be toxic in other ways.

Trials in animals first and then in humans are needed to eliminate this possibility.

What did the research involve?

The researchers performed a variety of experiments on human breast cancer stem cells. These are cells that are able to divide and become any type of cell the tumour needs in order to grow.

Cancer stem cells are different from most normal cells in that they can produce energy from glucose through a variety of pathways. This is one of the reasons they're able to grow and replicate better than normal cells.

Most also have an increased number of mitochondria – the powerhouse of cells – which can convert glucose into energy using oxygen. And one of the side effects of doxycycline is it inhibits the production of proteins required by mitochondria.

Previous research has suggested that by stopping the protein production, doxycycline could kill the cancer cells because they wouldn't be able to make energy.

But because cancer cells are good at adapting, there were concerns that some cancer cells would become drug resistant by using a different pathway to create energy, such as glycolysis.

This happens when certain cells, such as muscles, continue to work hard without oxygen, producing a build-up of lactic acid, and doesn't require oxygen or mitochondria.

This study looked at whether two natural products and six different drugs already approved for use in humans could kill cancer cells reliant on making energy using glycolysis – or in other words, kill the cancer cells that had resisted the initial treatment with doxycycline.

The natural products were vitamin C and berberine, a type of salt found in many plants.

The drugs included:
- chloroquine (antimalarial)
- atovaquone
- irinotecan
- sorafenib
- niclosamide
- stiripentol

What were the basic results?

Doxycycline reduced the cancer cells' ability to use different energy pathways. It did this by supressing the production of proteins important for mitochondrial function.

This wiped out many cancer cells, although some did became drug resistant. The doxycycline-resistant cells were then mostly reliant on the glycolysis pathway for energy production.

All of the drugs and natural products had some success in preventing these doxycycline-resistant cancer stem cells dividing. Vitamin C was the most successful.

The cells were 4-10 times more sensitive to vitamin C than cancer cells not resistant to doxycycline.

How did the researchers interpret the results?

The researchers concluded that doxycycline can kill some cancer cells and make others reliant on one energy pathway: glycolysis.

The doxycycline-resistant cells are then susceptible to natural products like vitamin C and drugs including chloroquine.

This, they say, "suggest[s] a new synthetic lethal strategy of i) doxycycline (to target mitochondria) and ii) vitamin C (to target glycolysis)."

Conclusion

This isn't the first time vitamin C has been studied for use against cancer: it has previously been shown to kill cancer cells in the laboratory and stop cancer growth in mice.

This new two-pronged approach may well prove to be useful in eradicating cancer stem cells in humans, but robust clinical trials are necessary first as cells can behave very differently in a laboratory environment.

Although all the drugs and natural products used in this study are already approved for use in humans, we don't know for certain what concentration would be required to obtain similar effects without being toxic.

This study also only looked at breast cancer stem cells. We don't know what effect the combination would have on other types of cancer cells, which stage of treatment this might be useful for, or for which types of cancer.