A recent high profile publication in Science Translational Medicine proposed that antioxidants might increase the rate of metastasis in mice models of melanoma.
NAC and the soluble vitamin E analog Trolox markedly increased the migration and invasive properties of human malignant melanoma cells but did not affect their proliferation. Both antioxidants increased the ratio between reduced and oxidized glutathione in melanoma cells and in lymph node metastases, and the increased migration depended on new glutathione synthesis. Furthermore, both NAC and Trolox increased the activation of the small guanosine triphosphatase (GTPase) RHOA, and blocking downstream RHOA signaling abolished antioxidant-induced migration. These results demonstrate that antioxidants and the system play a previously unappreciated role in malignant melanoma progression.
This goes against the common idea that anti-oxidants are cancer fighters!
So what is going on?
The answer, much like a Facebook relationship status, is “its complicated”. In fact anti-oxidants can have a wide range of effects on cells, including mitosis. Many “dietary antioxidants Resveratrol and Fisetin (found in red wine), inhibit Cdks, induce a G2 arrest and prevent entry into mitosis” (Burgess et al 2014). Furthermore, we recently showed that partial inhibition of Cdk1 can dramatically disrupt to mitosis. This caused increase cancer cell death… but also increased the rate of chromosome mis-segergations. (McCloy et al 2014). These mitotic errors can drive chromosome instability (CIN), which inturn can lead to the evolution of more aggressive, invasive tumours. Understanding the genetic background of each individual cancer will be key to determining why some cancer cells die and others thrive when given antioxidants.
If you would like to know more on how common stresses such as oxidation can disrupt mitosis, you can read our recent review Stressing Mitosis to Death.
Until then, if you have cancer and are thinking of taking antioxidants, make sure you consult your oncologist as they can significantly affect the efficacy of some chemotherapeutics, and hence maybe doing more harm than good.
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This entry was posted in News and tagged anti-oxidants, antioxidants, Cancer, Cdk, cell division, chemotherapeutics, chromosome instability, Fisetin, glutathione, Kinghorn Cancer Center, metaphase, Mitosis, Resveratrol.