Inhibition of Nox1 induces apoptosis by attenuating the AKT signaling pathway in oral squamous cell carcinoma cell lines.
NADPH oxidases, also known as the Nox family, are major sources of reactive oxygen species generation that regulate redox-sensitive signaling pathways. Recent studies have implicated the Nox family in cancer development and progression. However, the involvement of its members in the development of oral squamous cell carcinoma (OSCC) remains to be elucidated. To clarify this issue, we first analyzed mRNA expression of Nox/Duox family members (Nox1, Nox2, Nox3, Nox4, Nox5, Duox1 and Duox2) in five OSCC cell lines. Nox1 and Nox4 mRNAs were highly expressed in four OSCC cell lines. Western blot analysis revealed that the protein expression level of Nox1 was higher than that of Nox4 in the OSCC cell lines. In addition, knockdown of Nox1, but not Nox4, significantly suppressed cell viability and induced apoptosis in the HSC-2 and HSC-3 cells. We also found that a specific AKT inhibitor, perifosine, dose-dependently suppressed OSCC cell growth. Notably, Nox1 knockdown significantly attenuated the phosphorylation level of AKT. Furthermore, both Nox1 knockdown and perifosine treatment markedly enhanced the cisplatin-induced cytotoxic effect. Taken together, our results highlight that the Nox1/AKT signaling pathway plays an important role in cell survival in OSCC cells.
Department of Oral and Maxillofacial Surgery, Aichi Medical University Hospital, Aichi 480-1195, Japan.
Kunihiro
K
Ito
Department of Biochemistry, Aichi Medical University School of Medicine, Aichi 480-1195, Japan.
Akinobu
A
Ota
Department of Oral and Maxillofacial Surgery, Aichi Medical University Hospital, Aichi 480-1195, Japan.
Takayuki
T
Ono
Department of Oral and Maxillofacial Surgery, Aichi Medical University Hospital, Aichi 480-1195, Japan.
Toshiki
T
Nakaoka
Department of Biochemistry, Aichi Medical University School of Medicine, Aichi 480-1195, Japan.
Md
M
Wahiduzzaman
Department of Biochemistry, Aichi Medical University School of Medicine, Aichi 480-1195, Japan.
Sivasundaram
S
Karnan
Department of Biochemistry, Aichi Medical University School of Medicine, Aichi 480-1195, Japan.
Hiroyuki
H
Konishi
Department of Oral and Maxillofacial Surgery, Aichi Medical University Hospital, Aichi 480-1195, Japan.
Akifumi
A
Furuhashi
Department of Oral and Maxillofacial Surgery, Aichi Medical University Hospital, Aichi 480-1195, Japan.
Tomio
T
Hayashi
Department of Oral and Maxillofacial Surgery, Aichi Medical University Hospital, Aichi 480-1195, Japan.
Yoichi
Y
Yamada
Department of Biochemistry, Aichi Medical University School of Medicine, Aichi 480-1195, Japan.
Yoshitaka
Y
Hosokawa
Department of Oral and Maxillofacial Surgery, Aichi Medical University Hospital, Aichi 480-1195, Japan.
Yoshiaki
Y
Kazaoka
D017209:Apoptosis / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D019070:Cell Lineage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases / Q000096:biosynthesis* / Q000235:genetics; D051058:Oncogene Protein v-akt / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases; C402799:NOX1 protein, human; D051058:Oncogene Protein v-akt