Aspirin induces apoptosis in YD-8 human oral squamous carcinoma cells through activation of caspases, down-regulation of Mcl-1, and inactivation of ERK-1/2 and AKT.

NSAIDs and COX-2 inhibitors show anti-cancer activities in many cancer cells. In this study, we investigated the effects of NSAIDs (aspirin or indomethacin) and COX-2 inhibitor (NS-398) on growth of YD-8 human oral squamous carcinoma cells. Interestingly, among drugs tested, aspirin showed strongest inhibitory effects on viability and survival of YD-8 cells. Profoundly, aspirin treatment resulted in severe cell shrinkage and nuclear DNA fragmentation in YD-8 cells, suggesting the aspirin-induced apoptosis in YD-8 cells. Data of Western blot further demonstrated that aspirin treatment caused activation of caspases, down-regulation of Mcl-1 protein, dephosphorylation of ERK-1/2 and AKT, and also IkappaB-alpha proteolysis-dependent NF-kappaB activation in YD-8 cells. Aspirin, however, had no effect on expressions of Bcl-2, XIAP, and HIAP-1 in YD-8 cells. Importantly, pretreatment with z-VAD-fmk, a pan-caspase inhibitor blocked the aspirin-induced apoptosis and Mcl-1 down-regulation in YD-8 cells. These findings collectively suggest that aspirin induces apoptosis in YD-8 cells and the induction may be correlated to activation of caspases, caspase-dependent Mcl-1 proteolysis, inactivation of ERK-1/2 and AKT, and activation of NF-kappaB. It is suggested that aspirin may be applied a potential anti-cancer drug against human oral squamous carcinoma. Copyright (c) 2010 Elsevier Ltd. All rights reserved.