Cancer cells tricked into defective reproduction

Scientists at the University of Salford have successfully trialled a method of tricking cancer stem cells into manufacturing new cells with no power source, like cars without engines.

A ‘triple combination’ of vitamin C and two standard antibiotics — doxycycline and azithromycin — was sufficient to reduce stem cell growth by more than 90% in laboratory tests, according to research published in the journal Aging. Professor Michael Lisanti likened the process to “creating a factory recall on a grand scale”, noting that the cells “can’t generate any energy, so they can’t proliferate”.

Cancer stem-like cells are thought to be the root cause of chemotherapy resistance, leading to treatment failure in patients with advanced disease and the trigger of tumour recurrence and metastasis (regrowth and secondary cancer). The Salford team’s research focuses on the energetics of cancer stem cells — the processes that allow the cells to live and thrive — with a view to disrupting their metabolism.

Together with Professor Federica Sotgia, Prof Lisanti carried out trials in 2018 of the antibiotic doxycycline on cancer recurrence in hospital patients, resulting in a 40% reduction in cancer stem cells in patients, with a near 90% response rate. But while a 40% reduction was encouraging, Prof Lisanti said he was “interested in the other 60%, so we’re interested in new drug combinations to maximise the effects of the doxycycline”.

“Once we saw doxycycline was effective at targeting mitochondria within stem cells, the challenge was on to find an even more effective combination which we believe we have found with azithromycin.”

In laboratory tests, they found the two antibiotics could be used to target the production of 13 key mitochondrial proteins, which cuts off the fuel supply in the stem cells. And they found that vitamin C, acting as a mild pro-oxidant, amplifies the effects.

“What this combination does is speed up the production of new mitochondria but at the same time makes them functionally inactive — so new mitochondria are unable to generate ATP, the currency of the cell,” explained Prof Sotgia.

“It’s like making thousands of new cars without the necessary engine parts. They don’t work.”

The team emphasised that their combination is cheap and readily available and, because the doses of antibiotics are small (1 µM), the method avoids the potential problem of antibiotic resistance.

Image credit: ©stock.adobe.com/au/royaltystockphoto

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