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.
Park
In-Sook
IS
Department of Dentistry, School of Medicine, Keimyung University, 194 Dongsan-dong, Jung-gu, Daegu 700-712, Republic of Korea.
Jo
Jeong-Rang
JR
Hong
Hua
H
Nam
Ki-Young
KY
Kim
Jong-Bae
JB
Hwang
Sang-Hee
SH
Choi
Mi-Sun
MS
Ryu
Nam-Hee
NH
Jang
Hyun-Jung
HJ
Lee
Sang-Han
SH
Kim
Chin-Soo
CS
Kwon
Tae-Geon
TG
Park
Gy-Young
GY
Park
Jong-Wook
JW
Jang
Byeong-Churl
BC
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
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