Do Anti-Cancer Drugs Increase Intracellular Oxidative Stress?

Annually, 400,000 adolescents and children develop cancer, making it a leading cause of deaths for those under the age of 20. 

Anthracyclines (such as doxorubicin and daunorubicin) are commonly used drugs to treat childhood cancers. These drugs kill cancer cells, but it is not clear how. It could be they increase levels of highly damaging molecules called Reactive Oxygen Species, leading to a condition known as oxidative stress. However, no studies have measured this directly, so we aimed to determine whether doxorubicin and daunorubicin (1) kill and (2) increase oxidative stress in cancer cells. Anthracyclines also lead to side effects like heart failure, but it is not clear why. As such, we also determined whether doxorubicin and daunorubicin can kill heart cells. 

In this study cancer and heart cells were exposed to doxorubicin and daunorubicin. We measured cancer cell death and levels of oxidative stress using specialised equipment. 

Doxorubicin and daunorubicin killed cancer and heart cells. Cell death was dependent on the concentration and time cells were exposed to the drugs. Doxorubicin and daunorubicin also prevented cancer cells from growing. Both drugs increased levels of oxidative stress in cancer cells, however the effect of doxorubicin was greater. 

Our findings confirm that anthracyclines kill cancer cells. We are also the first to directly show that anthracyclines increased oxidative stress in these cells. This suggests the anti-cancer actions of these drugs are at least partially dependent on oxidative stress. Our findings also suggest that heart failure caused by anthracyclines may be caused by a loss of heart cells.