ISLAMABAD: A combination of vitamin C and antibiotics could be key to killing cancer stem cells, a new study finds, paving the way for a strategy that could combat cancer recurrence and treatment resistance. Study co-author Prof. Michael Lisanti, of the Biomedical Research Centre at the University of Salford in the United Kingdom, and colleagues recently reported their findings in the journal Oncotarget. Stem cells are cells that have the ability to reproduce and transform into other cell types. Studies have suggested that some cancer cells act in a similar way to stem cells, reproducing in order to form and sustain tumors. These CSCs are believed to be a main driver behind the growth, spread, and recurrence of tumors among patients with advanced cancer, and they also play a role in resistance to cancer therapy. The new study builds on those findings, showing that the CSC-killing capabilities of vitamin C can be increased with the help of antibiotics. To reach their results, the researchers administered Doxycycline – an antibiotic used to treat acne, pneumonia, and other infections – to CSCs in increasing doses over 3 months. The team explains that the antibiotic induces “metabolic flexibility,” meaning that it inhibits the cells’ ability to switch fuel sources as a means of survival. As a result, the cells are left with just glucose as a source of energy. However, by following up Doxycycline administration with doses of vitamin C, the researchers were also able to remove glucose from CSCs – a “second punch” that effectively starves the cells to death. “In this scenario, vitamin C behaves as an inhibitor of glycolysis, which fuels energy production in mitochondria, the ‘powerhouse’ of the cell,” explains study co-author Dr. Federica Sotgia, also of the Biomedical Research Centre at the University of Salford. The previous research from the team found that vitamin C alone was up to 10 times more effective for killing CSCs than 2-DG. However, adding Doxycycline to the therapy made it almost 100 times more effective. What is more, the researchers identified a further eight compounds that could be administered after Doxycycline to deliver the “second punch” to CSCs. “This is further evidence that vitamin C and other non-toxic compounds may have a role to play in the fight against cancer,” says Prof. Lisanti. Prof. Michael Lisanti said that “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.” Arthritis drug: A drug currently being trialed for the treatment of rheumatoid arthritis has the potential to be the first ever drug to prevent aortic valve stenosis, a common and deadly heart condition Aortic valve stenosis may be caused by aortic valve calcification, a condition characterized by a build-up of calcium deposits in the aortic valve of the heart, which is most common among older adults. Calcification can cause the aortic valve to narrow or stiffen. This can lead to stenosis, whereby blood flow through the opening of the aortic valve is restricted. As a result, the heart needs to work harder in order to push blood through the aortic valve opening, which may cause the left ventricle to enlarge and thicken. Left untreated, aortic valve stenosis can lead to irregular heart rhythm (known as arrhythmia), cardiac arrest, and heart failure. At present, an aortic valve repair or replacement is only way to eradicate aortic valve stenosis. But the new study may have discovered a way to prevent the condition, possibly eliminating the need for surgery. For their study, Prof. Merryman and colleagues focused on a protein called cadherin-11 (CDH-11). This protein – produced by cells called fibroblasts, which are present in heart valves – is essential for wound healing, but recent studies have shown that it also plays a key role in aortic valve stenosis. The researchers explain that as the heart ages, fibroblasts become overactive and produce excessive amounts of CDH-11, which leads to inflammation of the aortic valve. The team first began investigating the role of CDH-11 in 2013, when they came across two studies that inadvertently demonstrated how activating and deactivating the protein could control fibroblast activity and cellular calcification. For this latest study, the researchers tested the effects of an anti-inflammatory drug called SYN0012, which binds to CDH-11 on the cell surface of aortic valves. The researchers found that SYN0012 stops fibroblasts from becoming overactive, which prevents CDH-11 overproduction and aortic valve inflammation. Based on these findings, the team believes that SYN0012 could stop aortic valve stenosis in its tracks. “The exciting thing about this drug’s potential is that it could allow us to consider a strategy of prevention, as we do with other forms of heart disease – like lowering cholesterol or using ACE inhibitors. We don’t have any interventions for aortic valve stenosis that slow its progression.” Study co-author Mike Baker, Vanderbilt University Once SYN0012 has been through human clinical trials for the treatment of rheumatoid arthritis, Prof. Merryman and colleagues plan to test its safety and efficacy for the treatment of aortic valve stenosis. If successful, the drug could one day eliminate the need for aortic valve replacements.