title: 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.
abstract: 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.
authors.affiliation: Department of Dentistry, School of Medicine, Keimyung University, 194 Dongsan-dong, Jung-gu, Daegu 700-712, Republic of Korea.
authors.forename: In-Sook
authors.initials: IS
authors.lastname: Park
authors.forename: Jeong-Rang
authors.initials: JR
authors.lastname: Jo
authors.forename: Hua
authors.initials: H
authors.lastname: Hong
authors.forename: Ki-Young
authors.initials: KY
authors.lastname: Nam
authors.forename: Jong-Bae
authors.initials: JB
authors.lastname: Kim
authors.forename: Sang-Hee
authors.initials: SH
authors.lastname: Hwang
authors.forename: Mi-Sun
authors.initials: MS
authors.lastname: Choi
authors.forename: Nam-Hee
authors.initials: NH
authors.lastname: Ryu
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Jang
authors.forename: Sang-Han
authors.initials: SH
authors.lastname: Lee
authors.forename: Chin-Soo
authors.initials: CS
authors.lastname: Kim
authors.forename: Tae-Geon
authors.initials: TG
authors.lastname: Kwon
authors.forename: Gy-Young
authors.initials: GY
authors.lastname: Park
authors.forename: Jong-Wook
authors.initials: JW
authors.lastname: Park
authors.forename: Byeong-Churl
authors.initials: BC
authors.lastname: Jang
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D001241:Aspirin / Q000633:toxicity*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D020169:Caspases / Q000378:metabolism*; D002452:Cell Count; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors*; D006801:Humans; D009062:Mouth Neoplasms / Q000473:pathology*; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D016328:NF-kappa B / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors*; D011401:Promoter Regions, Genetic / Q000235:genetics; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D016328:NF-kappa B; D047428:Protein Kinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D051058:Oncogene Protein v-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D020169:Caspases; D001241:Aspirin