antioxidants

AntiOxidants and Cancer: A complicated story

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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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Anti-Oxaidants and Cancer…A complicated story!

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There has been a bit of press lately suggesting that Antioxidants might actually be bad for cancer… not good as they are commonly promoted in the media.
IFLS has put together a great article on some of the reasons why antioxidants might not be such a great thing [Link].

In addition, we recently wrote a review article about how different ‘stresses’ including oxidation can affect mitosis, and cancer. We also came to a similar conclusion in our review,  that antioxidants were a complicated and not always benifical for treating cancer. One of the main reason we suggested this was due to the fact that many common antioxidants are part of the Flavonoid family. On the surface that sound great, but many Flavonoids also happen to potently inhibit cyclin dependent kinases (Cdks). Coincidentally, our other recent article in Cell Cycle, showed that partial inhibition of Cdk1 can dramatically disrupt mitosis and drive severe cytokinesis defects and polyploidy (see video below). These mitotic defects are the foundation of chromosome instability  (CIN), which is a hallmark of more aggressive cancer types, that are also resistant to most chemotherapies and treatments. In simple terms, there is a possibility that in some cases, taking large quantities of dietary Flavonoids (e.g red wine, dark chocolate etc) could drive the formation of more aggressive cancers. This is definitely an area that needs a lot more research, and as always make sure that you fully discuss any dietary and supplements with your oncologist.

 

This is what happens when a ‘fairly normal’ cancer cell is treated with low doses of a Cdk1 inhibitor.

Here is a picture of a polyploid cancer cell, which was produced by partially inhibiting Cdk1.

ImageJ=1.48f unit=micron