Down-regulation of S-phase kinase associated protein 2 (Skp2) induces apoptosis in oral cancer cells.
S-phase kinase associated protein 2 (Skp2) is a member of an F-box family of substrate-recognition subunits of SCF ubiquitin-protein ligase complexes that has been implicated in the ubiquitin-mediated degradation of several key regulators of mammalian G1 progression, including the cyclin-dependent kinase inhibitor p27Kip1, a dosage-dependent tumor suppressor protein. The anti-sense effect was confirmed in two cell lines of oral cancer cells that also exhibited over-expression of the Skp2 protein. In this study, we examined the mechanism responsible for anti-sense-mediated growth inhibition of oral cancer cells in vitro and in vivo. Skp2-anti-sense treatment induced apoptosis characterized by an increase in the early apoptosis, fragmentation of nuclei and activation of caspase-3, -8 and -9. Moreover, the growth of xenograft tumors was markedly suppressed by Skp2-anti-sense treatment. Furthermore, histological specimen revealed apoptotic cell death was increased in Skp2-anti-sense treated tumors. Our results suggest that down-regulation of Skp2 appears to induce apoptosis in oral cancer cells, targeting this molecule could represent a promising new therapeutic approach for this type of cancer.
Harada
Koji
K
Second Department of Oral and Maxillofacial Surgery, School of Dentistry, University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770-8504, Japan. harako@dent.tokushima-u.ac.jp
Supriatno
Kawashima
Yuichiro
Y
Itashiki
Yasutaka
Y
Yoshida
Hideo
H
Sato
Mitsunobu
M
D000818:Animals; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002455:Cell Division; D053938:DNA Fragmentation; D004273:DNA, Neoplasm / Q000235:genetics; D015536:Down-Regulation; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D009368:Neoplasm Transplantation; D016376:Oligonucleotides, Antisense; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D044786:S-Phase Kinase-Associated Proteins; D020169:Caspases