Using vitamin C and the antibiotic doxycycline together was 100 times more effective in killing human CSCs in the lab than 2-DG, a potential anti-cancer agent currently being tested in clinical trials.
The researchers say that their findings help understand how combination therapies could be used to prevent cancer cells becoming drug-resistant.
'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,' said Professor Michael Lisanti at the University of Salford, who led the study. '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.'
These 'metabolically flexible' cells are CSCs, which reproduce to drive the growth, spread and recurrence of tumours. They also play a role in resistance to cancer therapy so targeting and killing these CSCs could potentially prevent tumour growth or recurrence.
Doxycycline can kill many CSCs by inhibiting the production of proteins required by mitochondria – the powerhouse of cells. However, because CSCs are very good at adapting, some become resistant to this effect of doxycycline by using a different pathway to create energy: glycolysis.
In the study, published in the journal Oncotarget, the researchers investigated whether two natural products (vitamin C and berberine) and six different drugs already approved for use in humans could kill doxycycline-resistant CSCs, by blocking glycolysis. All of the natural products and drugs prevented the doxycycline-resistant CSCs dividing, but vitamin C was the most successful.
The researchers propose a two-pronged approach to kill cancer stem cells: first doxycycline to target mitochondria, then vitamin C to target glycolysis.
'This is further evidence that vitamin C and other non-toxic compounds may have a role to play in the fight against cancer,' explained Profesor 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.'
Though these results are promising, cells can behave differently in humans than the laboratory, notes an analysis published by NHS Choices. Plus, despite both vitamin C and doxycycline being safe in humans, it's not yet clear how they interact with other cancer treatments or whether the doses required to kill cancer cells could be toxic. The analysis recommends more research – including robust clinical trials – before this approach can be recommended as a cancer treatment.