Prevention of fibroblast senescence by hyaluronic acid and clinical application to chemoradiation-induced oral mucositis

3^rd World Congress on Cancer Science & Therapy

October 21-23, 2013 DoubleTree by Hilton Hotel San Francisco Airport, CA, USA

Nicola Cirillo

ScientificTracks: J Cancer Sci Ther

Abstract :

Purpose:Virtually all patients receiving radio and chemotherapy for head and neck cancer develop oralmucositis (1), a severe and highly debilitating condition. Because the onset of mucositis is related to the production of reactive oxygen species (ROS) (2), here we investigated a possible protective effect of sodiumhyaluronate enriched with aminoacids (Mucosamin®) in the damage induced by oxidative stress bothin vitro and in vivo. Methods: Normaloralstromalfibroblasts (NOF) and keratinocytes (NOK) wereused for the in vitrostudy. Oxidative stress wasinduced with H2O2 and senescence markers were investigated by Western blot (p16),immunofluorescence (SA-bgal), andsenescence-associatedsecretory (SAS) molecules. Metaboliceffectson NOK werestudied by MTT test. The clinical study was a case-series of 11patients undergoing chemiotherapy, radiotherapy, or both. Sodiumhyaluronate spray (Mucosamin®) was used for this study. Results: Whilst H2O2 wastoxic to NOK and induced celldeath in vitro, exposure of NOF to H2O2 led to long termsenescence, asdemonstrated by sustained increase in the levels of p16 and Sab-gal and expression of SAS phenotype. Conditioned media from senescent NOF induced detrimental effects on NOK, asshown by MTT. Pre-treatment with Mucosamin® couldpreventboth H2O2- induced fibroblastsenescence and reduction of metabolicactivity of NOK exposed to the conditioned media. The data from case- series of 11 patients undergoing radio/chemotherapy demonstrated that prophylactic use of Mucosamin®preventedoralmucositis in 9 out of 11 patients; the remaining 2 showedlow grade transientmucositis; 10 out of 11 patients developed radiodermitis. Conclusion: SH preparations can preventcellularsenescence in NOF undergoingoxidative stress in vitro. Clinically, prophylactic use of SH virtually abrogates the incidence of oralmucositis secondary to chemoradiation, providing a safe and approachable intervention for this most debilitating condition.