by Carl Belger
Doxorubicin or DOX is an anti-cancer drug currently used to treat a variety of cancers. However, one of its common side effects is cardiotoxicity or damage to the heart. This is caused by heart cells dying during treatment and is commonly known as DOX-induced cardiotoxicity. Patients treated with DOX can experience heart disfunction anytime from a few hours after treatment to years later. DOX-induced cardiotoxicity has prompted the search for supplementary cardioprotective agents which could prevent heart damage and minimize side effects.
Please welcome to the stage: Sphingosine-1-phosphate AKA S1P. In a paper by Miguel Frias et al., it was successfully shown that S1P administered before DOX treatment caused fewer cells to die. But how exactly was this done, and, more importantly, can we trust the results? As usual with science, the answer is yes but also no.
Firstly, the researchers in this paper used cell culture experiments; essentially, they treated cells in a plastic dish with different reagents and measured how many cells lived and died. For this paper they used a type of heart cells called cardiomyocytes. The cardiomyocytes were treated with S1P, DOX, both, or neither and cell death was measured through something known as caspase3 activity. Caspase3 is an enzyme that is upregulated in cells undergoing cell death.
As you can see from the figure above, adding increased concentrations of S1P, progressively decreased the amount of cell death caused by DOX. This figure along with many others in the paper gave strong evidence for the cardioprotective qualities of S1P.
However, there are some important limitations to this paper. Firstly, and most obviously, cells in a dish do not accurately represent the human body and its complex functions; S1P may have a completely different affect in vivo. In addition to this, these experiments ignored one important factor related to DOX-induced cardiotoxicity: cancer. Patients who receive S1P and DOX will do so because they have cancer. Thus, it is important to recognize that their bodies will be affected by this. Perhaps further experiments could be performed on cardiomyocytes in a cancer environment to see if this affects the protective characteristics of S1P.
Overall this paper shed light on a potential drug that could help millions of cancer patients around the world. However, it is vital that we confirm its protective potential before we implement it as a common treatment.
Frias, Miguel A, Ursula Lang, Christine Gerber-Wicht, and Richard W James. 2010. “Native and Reconstituted HDL Protect Cardiomyocytes from Doxorubicin-Induced Apoptosis.” Cardiovascular Research 85 (1): 118–26. https://doi.org/10.1093/cvr/cvp289.