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Article

Oncotropic H-1 parvovirus infection degrades HIF-1α protein in human pancreatic cancer cells independently of VHL and RACK1

  • Authors:
    • Il-Rae Cho
    • Sirichat Kaowinn
    • Jeong Moon
    • Jiwon Soh
    • Ho Young Kang
    • Cho-Rok Jung
    • Sangtaek Oh
    • Hayne Song
    • Sang Seok Koh
    • Young-Hwa Chung
  • View Affiliations / Copyright

    Affiliations: BK21+, Department of Cogno-Mechatronics Engineering, Pusan National University, Busan 609-736, Republic of Korea, Department of Microbiology, Pusan National University, Busan 609-736, Republic of Korea, Gene Therapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-333, Republic of Korea, Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 136-702, Republic of Korea, Department of Biological Sciences, Dong-A University, Busan 604-714, Republic of Korea
  • Pages: 2076-2082
    |
    Published online on: March 9, 2015
       https://doi.org/10.3892/ijo.2015.2922
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Abstract

Overexpression of HIF-1α, a transcription factor responsive to hypoxia, is frequently observed in malignant tumors, which sometimes show resistance to chemotherapy and radiation therapy. Consequently, decrease of HIF-1α through virotherapy offers a logical strategy for the treatment of aggressive tumors. In this study, we found that infection with the oncolytic H-1 parvovirus decreased HIF-1α protein levels in pancreatic cancer cells under CoCl2 or hypoxia. The H-1 virus-induced decrease of HIF-1α was regulated by a proteasome-mediated pathway. Suppression of VHL, an E3 ligase and a critical regulator of HIF-1α, or enforced expression of UCP, an E2 ubiquitin-conjugating enzyme, failed to inhibit the H-1 virus-induced decrease of HIF-1α. Furthermore, siRNA-mediated suppression of RACK1, another regulator of HIF-1α, did not prevent H-1 viral infection from lowering HIF-1α protein levels. Although decrease of HIF-1α was observed after H-1 viral infection, constitutive expression of HIF-1α limited H-1 viral replication. After combined treatment with H-1 parvovirus and YC-1, an inhibitor of HIF-1α, the apoptosis of pancreatic cancer cells was greater than after treatment with H-1 virus alone or YC-1 alone. Accordingly, we propose that H-1 parvovirus could be used with YC-1 as a potential therapeutic agent against aggressive tumors exhibiting hypoxia and increased levels of HIF-1α.
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Copy and paste a formatted citation
Spandidos Publications style
Cho I, Kaowinn S, Moon J, Soh J, Kang HY, Jung C, Oh S, Song H, Koh SS, Chung Y, Chung Y, et al: Oncotropic H-1 parvovirus infection degrades HIF-1α protein in human pancreatic cancer cells independently of VHL and RACK1. Int J Oncol 46: 2076-2082, 2015.
APA
Cho, I., Kaowinn, S., Moon, J., Soh, J., Kang, H.Y., Jung, C. ... Chung, Y. (2015). Oncotropic H-1 parvovirus infection degrades HIF-1α protein in human pancreatic cancer cells independently of VHL and RACK1. International Journal of Oncology, 46, 2076-2082. https://doi.org/10.3892/ijo.2015.2922
MLA
Cho, I., Kaowinn, S., Moon, J., Soh, J., Kang, H. Y., Jung, C., Oh, S., Song, H., Koh, S. S., Chung, Y."Oncotropic H-1 parvovirus infection degrades HIF-1α protein in human pancreatic cancer cells independently of VHL and RACK1". International Journal of Oncology 46.5 (2015): 2076-2082.
Chicago
Cho, I., Kaowinn, S., Moon, J., Soh, J., Kang, H. Y., Jung, C., Oh, S., Song, H., Koh, S. S., Chung, Y."Oncotropic H-1 parvovirus infection degrades HIF-1α protein in human pancreatic cancer cells independently of VHL and RACK1". International Journal of Oncology 46, no. 5 (2015): 2076-2082. https://doi.org/10.3892/ijo.2015.2922
Copy and paste a formatted citation
x
Spandidos Publications style
Cho I, Kaowinn S, Moon J, Soh J, Kang HY, Jung C, Oh S, Song H, Koh SS, Chung Y, Chung Y, et al: Oncotropic H-1 parvovirus infection degrades HIF-1α protein in human pancreatic cancer cells independently of VHL and RACK1. Int J Oncol 46: 2076-2082, 2015.
APA
Cho, I., Kaowinn, S., Moon, J., Soh, J., Kang, H.Y., Jung, C. ... Chung, Y. (2015). Oncotropic H-1 parvovirus infection degrades HIF-1α protein in human pancreatic cancer cells independently of VHL and RACK1. International Journal of Oncology, 46, 2076-2082. https://doi.org/10.3892/ijo.2015.2922
MLA
Cho, I., Kaowinn, S., Moon, J., Soh, J., Kang, H. Y., Jung, C., Oh, S., Song, H., Koh, S. S., Chung, Y."Oncotropic H-1 parvovirus infection degrades HIF-1α protein in human pancreatic cancer cells independently of VHL and RACK1". International Journal of Oncology 46.5 (2015): 2076-2082.
Chicago
Cho, I., Kaowinn, S., Moon, J., Soh, J., Kang, H. Y., Jung, C., Oh, S., Song, H., Koh, S. S., Chung, Y."Oncotropic H-1 parvovirus infection degrades HIF-1α protein in human pancreatic cancer cells independently of VHL and RACK1". International Journal of Oncology 46, no. 5 (2015): 2076-2082. https://doi.org/10.3892/ijo.2015.2922
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