Month: October 2015
AntiOxidants and Cancer: A complicated story
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.
New Review Article Published!! “Mechanisms Regulating Phosphatase Specificity During Mitotic Exit”
Great News, we have a new review article that has just been published online today in Inside the Cell!
Its Open Access, so that means its free for everyone to read!
During mitotic exit, phosphatases reverse thousands of phosphorylation events in a specific temporal order to ensure that cell division occurs correctly. This review explores how the physicochemical properties of the phosphosite and surrounding amino acids affect interactions with phosphatase/s and help determine the dephosphorylation of individual phosphorylation sites during mitotic exit.
The Full Reference and link for the Article can be found below:
Samuel Rogers, Rachael McCloy, D Neil Watkins and Andrew Burgess Mechanisms regulating phosphatase specificity and the removal of individual phosphorylation sites during mitotic exit Inside the Cell [Link]
Position available: 2016 Honours Student Project in our Lab
Great news we are currently looking for a new honours student for 2016.
The title of the project is “Developing novel biosensors to monitor DNA damage in cancer cells”.
Its a very exciting new project incorporating cutting edge microscopy and fluorescent biosensors.
If you think you have what it takes and are interested please feel free contact myself, or UNSW SoMS.
For more information on the UNSW honours program please visit: http://medicalsciences.med.unsw.edu.au/students/soms-honours/
Below is an example of the images that will be created during the project.
