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

  • Published online on: March 9, 2015     https://doi.org/10.3892/ijo.2015.2922
  • Pages: 2076-2082
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


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.
View Figures
View References

Related Articles

Journal Cover

May-2015
Volume 46 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

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