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Article

Inhibition of Nox1 induces apoptosis by attenuating the AKT signaling pathway in oral squamous cell carcinoma cell lines

  • Authors:
    • Kunihiro Ito
    • Akinobu Ota
    • Takayuki Ono
    • Toshiki Nakaoka
    • Md. Wahiduzzaman
    • Sivasundaram Karnan
    • Hiroyuki Konishi
    • Akifumi Furuhashi
    • Tomio Hayashi
    • Yoichi Yamada
    • Yoshitaka Hosokawa
    • Yoshiaki Kazaoka
  • View Affiliations / Copyright

    Affiliations: Department of Oral and Maxillofacial Surgery, Aichi Medical University Hospital, Aichi 480-1195, Japan, Department of Biochemistry, Aichi Medical University School of Medicine, Aichi 480-1195, Japan
  • Pages: 2991-2998
    |
    Published online on: September 5, 2016
       https://doi.org/10.3892/or.2016.5068
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Abstract

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.
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1 

Parkin DM, Bray F, Ferlay J and Pisani P: Global cancer statistics, 2002. CA Cancer J Clin. 55:74–108. 2005. View Article : Google Scholar : PubMed/NCBI

2 

Sklenicka S, Gardiner S, Dierks EJ, Potter BE and Bell RB: Survival analysis and risk factors for recurrence in oral squamous cell carcinoma: Does surgical salvage affect outcome? J Oral Maxillofac Surg. 68:1270–1275. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Dissanayaka WL, Pitiyage G, Kumarasiri PV, Liyanage RL, Dias KD and Tilakaratne WM: Clinical and histopathologic parameters in survival of oral squamous cell carcinoma. Oral Surg Oral Med Oral Pathol Oral Radiol. 113:518–525. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Chen YK, Huang HC, Lin LM and Lin CC: Primary oral squamous cell carcinoma: An analysis of 703 cases in southern Taiwan. Oral Oncol. 35:173–179. 1999. View Article : Google Scholar : PubMed/NCBI

5 

Fioretti F, Bosetti C, Tavani A, Franceschi S and La Vecchia C: Risk factors for oral and pharyngeal cancer in never smokers. Oral Oncol. 35:375–378. 1999. View Article : Google Scholar

6 

Altieri A, Bosetti C, Gallus S, Franceschi S, Dal Maso L, Talamini R, Levi F, Negri E, Rodriguez T and La Vecchia C: Wine, beer and spirits and risk of oral and pharyngeal cancer: A case-control study from Italy and Switzerland. Oral Oncol. 40:904–909. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Kolanjiappan K, Ramachandran CR and Manoharan S: Biochemical changes in tumor tissues of oral cancer patients. Clin Biochem. 36:61–65. 2003. View Article : Google Scholar : PubMed/NCBI

8 

Kaur J, Politis C and Jacobs R: Salivary 8-hydroxy-2-deoxyguanosine, malondialdehyde, vitamin C, and vitamin E in oral pre-cancer and cancer: diagnostic value and free radical mechanism of action. Clin Oral Investig. 20:315–319. 2016. View Article : Google Scholar

9 

Block K and Gorin Y: Aiding and abetting roles of NOX oxidases in cellular transformation. Nat Rev Cancer. 12:627–637. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Weyemi U, Redon CE, Parekh PR, Dupuy C and Bonner WM: NADPH oxidases NOXs and DUOXs as putative targets for cancer therapy. Anticancer Agents Med Chem. 13:502–514. 2013.

11 

Sancho P and Fabregat I: NADPH oxidase NOX1 controls autocrine growth of liver tumor cells through up-regulation of the epidermal growth factor receptor pathway. J Biol Chem. 285:24815–24824. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Momose F, Araida T, Negishi A, Ichijo H, Shioda S and Sasaki S: Variant sublines with different metastatic potentials selected in nude mice from human oral squamous cell carcinomas. J Oral Pathol Med. 18:391–395. 1989. View Article : Google Scholar : PubMed/NCBI

13 

Nakaoka T, Ota A, Ono T, Karnan S, Konishi H, Furuhashi A, Ohmura Y, Yamada Y, Nakaoka T, Ota A, Ono T, Karnan S, Konishi H, Furuhashi A, Ohmura Y, Yamada Y, Hosokawa Y and Kazaoka Y: Combined arsenic trioxide-cisplatin treatment enhances apoptosis in oral squamous cell carcinoma cells. Cell Oncol. 37:119–129. 2014. View Article : Google Scholar

14 

Hossain E, Ota A, Karnan S, Damdindorj L, Takahashi M, Konishi Y, Konishi H and Hosokawa Y: Arsenic augments the uptake of oxidized LDL by upregulating the expression of lectin-like oxidized LDL receptor in mouse aortic endothelial cells. Toxicol Appl Pharmacol. 273:651–658. 2013. View Article : Google Scholar : PubMed/NCBI

15 

Takahashi M, Ota A, Karnan S, Hossain E, Konishi Y, Damdindorj L, Konishi H, Yokochi T, Nitta M and Hosokawa Y: Arsenic trioxide prevents nitric oxide production in lipopolysac-charide -stimulated RAW 264.7 by inhibiting a TRIF-dependent pathway. Cancer Sci. 104:165–170. 2013. View Article : Google Scholar

16 

Ralph SJ, Rodríguez-Enríquez S, Neuzil J, Saavedra E and Moreno-Sánchez R: The causes of cancer revisited: 'mitochondrial malignancy' and ROS-induced oncogenic transformation - why mitochondria are targets for cancer therapy. Mol Aspects Med. 31:145–170. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Mochizuki T, Furuta S, Mitsushita J, Shang WH, Ito M, Yokoo Y, Yamaura M, Ishizone S, Nakayama J, Konagai A, et al: Inhibition of NADPH oxidase 4 activates apoptosis via the AKT/apoptosis signal-regulating kinase 1 pathway in pancreatic cancer PANC-1 cells. Oncogene. 25:3699–3707. 2006. View Article : Google Scholar : PubMed/NCBI

18 

Tanaka M, Miura Y, Numanami H, Karnan S, Ota A, Konishi H, Hosokawa Y and Hanyuda M: Inhibition of NADPH oxidase 4 induces apoptosis in malignant mesothelioma: Role of reactive oxygen species. Oncol Rep. 34:1726–1732. 2015.PubMed/NCBI

19 

Zhang B, Liu Z and Hu X: Inhibiting cancer metastasis via targeting NAPDH oxidase 4. Biochem Pharmacol. 86:253–266. 2013. View Article : Google Scholar : PubMed/NCBI

20 

Puca R, Nardinocchi L, Starace G, Rechavi G, Sacchi A, Givol D and D'Orazi G: Nox1 is involved in p53 deacetylation and suppression of its transcriptional activity and apoptosis. Free Radic Biol Med. 48:1338–1346. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Fletcher EV, Love-Homan L, Sobhakumari A, Feddersen CR, Koch AT, Goel A and Simons AL: EGFR inhibition induces proinflammatory cytokines via NOX4 in HNSCC. Mol Cancer Res. 11:1574–1584. 2013. View Article : Google Scholar : PubMed/NCBI

22 

Orcutt KP, Parsons AD, Sibenaller ZA, Scarbrough PM, Zhu Y, Sobhakumari A, Wilke WW, Kalen AL, Goswami P, Miller FJ Jr, et al: Erlotinib-mediated inhibition of EGFR signaling induces metabolic oxidative stress through NOX4. Cancer Res. 71:3932–3940. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Fumarola C, Bonelli MA, Petronini PG and Alfieri RR: Targeting PI3K/AKT/mTOR pathway in non small cell lung cancer. Biochem Pharmacol. 90:197–207. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Barrett D, Brown VI, Grupp SA and Teachey DT: Targeting the PI3K/AKT/mTOR signaling axis in children with hematologic malignancies. Paediatr Drugs. 14:299–316. 2012.PubMed/NCBI

25 

Simpson DR, Mell LK and Cohen EE: Targeting the PI3K/AKT/mTOR pathway in squamous cell carcinoma of the head and neck. Oral Oncol. 51:291–298. 2015. View Article : Google Scholar

26 

Kozaki K, Imoto I, Pimkhaokham A, Hasegawa S, Tsuda H, Omura K and Inazawa J: PIK3CA mutation is an oncogenic aberration at advanced stages of oral squamous cell carcinoma. Cancer Sci. 97:1351–1358. 2006. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Ito K, Ota A, Ono T, Nakaoka T, Wahiduzzaman M, Karnan S, Konishi H, Furuhashi A, Hayashi T, Yamada Y, Yamada Y, et al: Inhibition of Nox1 induces apoptosis by attenuating the AKT signaling pathway in oral squamous cell carcinoma cell lines. Oncol Rep 36: 2991-2998, 2016.
APA
Ito, K., Ota, A., Ono, T., Nakaoka, T., Wahiduzzaman, M., Karnan, S. ... Kazaoka, Y. (2016). Inhibition of Nox1 induces apoptosis by attenuating the AKT signaling pathway in oral squamous cell carcinoma cell lines. Oncology Reports, 36, 2991-2998. https://doi.org/10.3892/or.2016.5068
MLA
Ito, K., Ota, A., Ono, T., Nakaoka, T., Wahiduzzaman, M., Karnan, S., Konishi, H., Furuhashi, A., Hayashi, T., Yamada, Y., Hosokawa, Y., Kazaoka, Y."Inhibition of Nox1 induces apoptosis by attenuating the AKT signaling pathway in oral squamous cell carcinoma cell lines". Oncology Reports 36.5 (2016): 2991-2998.
Chicago
Ito, K., Ota, A., Ono, T., Nakaoka, T., Wahiduzzaman, M., Karnan, S., Konishi, H., Furuhashi, A., Hayashi, T., Yamada, Y., Hosokawa, Y., Kazaoka, Y."Inhibition of Nox1 induces apoptosis by attenuating the AKT signaling pathway in oral squamous cell carcinoma cell lines". Oncology Reports 36, no. 5 (2016): 2991-2998. https://doi.org/10.3892/or.2016.5068
Copy and paste a formatted citation
x
Spandidos Publications style
Ito K, Ota A, Ono T, Nakaoka T, Wahiduzzaman M, Karnan S, Konishi H, Furuhashi A, Hayashi T, Yamada Y, Yamada Y, et al: Inhibition of Nox1 induces apoptosis by attenuating the AKT signaling pathway in oral squamous cell carcinoma cell lines. Oncol Rep 36: 2991-2998, 2016.
APA
Ito, K., Ota, A., Ono, T., Nakaoka, T., Wahiduzzaman, M., Karnan, S. ... Kazaoka, Y. (2016). Inhibition of Nox1 induces apoptosis by attenuating the AKT signaling pathway in oral squamous cell carcinoma cell lines. Oncology Reports, 36, 2991-2998. https://doi.org/10.3892/or.2016.5068
MLA
Ito, K., Ota, A., Ono, T., Nakaoka, T., Wahiduzzaman, M., Karnan, S., Konishi, H., Furuhashi, A., Hayashi, T., Yamada, Y., Hosokawa, Y., Kazaoka, Y."Inhibition of Nox1 induces apoptosis by attenuating the AKT signaling pathway in oral squamous cell carcinoma cell lines". Oncology Reports 36.5 (2016): 2991-2998.
Chicago
Ito, K., Ota, A., Ono, T., Nakaoka, T., Wahiduzzaman, M., Karnan, S., Konishi, H., Furuhashi, A., Hayashi, T., Yamada, Y., Hosokawa, Y., Kazaoka, Y."Inhibition of Nox1 induces apoptosis by attenuating the AKT signaling pathway in oral squamous cell carcinoma cell lines". Oncology Reports 36, no. 5 (2016): 2991-2998. https://doi.org/10.3892/or.2016.5068
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