Congratulations to Yap Wei Ney, PhD student from Dr Alan Prem Kumar’s lab, for receiving the Educational Fellowship Award from the European Academy of Dermatology Venereology (EADV). With the award she will attend the XV World Congress on Cancers of the Skin in Edinburgh, 3-6 September 2014.

Title: Preclinical Evidence for ?-tocotrienol, a Natural Vitamin E Constituent Ameliorates UVB-mediated DNA Damage and Impedes Skin Inflammatory and Photo-aging Processes

Tocotrienol (T3) is a less abundant and poorly studied form of vitamin E member. It has, for decades, been overshadowed by tocopherol (TP), the more common form of vitamin E, particularly alpha-tocopherol (?TP). However, recent in vitro and in vivo studies have convincingly shown that T3 possesses stronger biological properties than ?TP due to its three double bond at the farnesyl side chain. In this study, we elucidated apparent disparity of photo-protection between gamma-tocotrienol (?T3) and ?TP by different administration routes (oral and topical) in a chronic mouse model, which is physiologically and pathologically relevant.

MTT cell viability assay and flow cytometry were carried out to study UVB-induced cell cytotoxicity and apoptosis. Single (SSB) and double strand breaks (DSB) of DNA were investigated using immunofluorescence and western blotting. Oxidative stress and inflammatory markers were detected by ELISA. HPLC was used to quantify vitamin E uptake. SKH-1 hairless mice were UVB-irradiated for 30 weeks in this skin cancer prevention study. Two different delivery systems were studied to compare the disparity of the photo-protective effect of ?T3 and ?TP.

Among eight isomers of vitamin E, ?T3 exerted the most potent agent in protecting UVB-induced cytotoxicity and apoptosis in HaCaT and CCD1106 epidermal keratinocyte cells. ?T3 demonstrated to repair SSB and DSB more efficiently than ?TP by suppressing UVB-induced DNA lesion (CPD and 6,4-PP) and dephosphorylated histone H2AX at a lower dose and in a shorter time dependent. ?T3 was found to be more effective than ?TP to mitigate elevated levels of oxidative stress markers (8-OHdG, MDA and protein carbonyl) as well as inflammatory markers (IL-6, IL-8 and COX-2) upon UVB irradiation. 2% of ?T3 formulated cream shown to prevent UVB-exposed epidermal hyperplasia at 24 weeks. It is noteworthy that ?T3-treated cohort in both administration routes demonstrated splenomegaly protection statistically significant with lower granulocytes infiltration in spleen. This may be ascribed to high intracellular uptake of ?T3 by skin cells.

This study is therefore expected to unravel a novel role for ?T3 in dermatology, and consequently position it as a superior vitamin E for the prevention of UVB-induced photo-aging and skin cancers.

Authors:

Wei Ney Yap^1,2,3, Gautam Sethi^1,3, Chee Wai Fong², Alan Prem Kumar^1,3,4,5

• ¹Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore 2Davos Life Science Pte Ltd, Singapore
• ³Cancer Science Institute of Singapore, National University of Singapore
• ⁴School of Biomedical Sciences, Faculty of Health Sciences, Curtin University, Western Australia
• ⁵Department of Biological Sciences, University of North Texas, Denton, TX, US