Comparison of UVB and UVC effects on the DNA damage-response protein 53BP1 in human pancreatic cancer

Fuminari Uehara, Shinji Miwa, Yasunori Tome, Yukihiko Hiroshima, Shuya Yano, Mako Yamamoto, Elena Efimova, Yasunori Matsumoto, Hiroki Maehara, Michael Bouvet, Fuminori Kanaya, Robert M. Hoffman

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13 Citations (Scopus)

Abstract

We have previously demonstrated that ultraviolet (UV) light is effective against a variety of cancer cells expressing fluorescent proteins in vivo as well as in vitro. In the present report, we compared the DNA damage repair (DDR) response of pancreatic cancer cells after UVB or UVC irradiation. The UV-induced DNA damage repair was imaged with green fluorescent protein (GFP) fused to the DDR-related chromatin-binding protein 53BP1 in MiaPaCa-2 human pancreatic cancer cells growing in 3D Gelfoam® histoculture and in superficial tumors grown in nude mice. 53BP1-GFP forms foci during DNA damage repair. A clonogenic assay in 2D monolayer culture initially showed that UVC and UVB inhibited MiaPaCa-2 cell proliferation in a dose-dependent manner, with UVC having more efficacy. Three-dimensional Gelfoam® histocultures and confocal imaging enabled 53BP1-GFP foci to be observed within 1 h after UV irradiation, indicating the onset of DDR response. UVB-induced 53BP1-GFP focus formation was observed up to a depth of 120 μm in MiaPaCa-2 cells on Gelfoam® compared to 80 μm for UVC. UVB-induced 53BP1-GFP focus formation was observed up to a depth of 80 μm in MiaPaCa-2 cells, implanted within skin flaps in mice, at a significantly greater extent than UVC. MiaPaCa-2 cells irradiated by UVB or UVC in the skin-flap mouse model had a significant decrease in tumor growth compared to untreated controls with UVB having more efficacy than UVC. Our results demonstrate that UVB has greater tissue penetration than UVC because of its longer wavelength and has clinical potential for eradicating superficial cancer.

Original languageEnglish
Pages (from-to)1724-1728
Number of pages5
JournalJournal of Cellular Biochemistry
Volume115
Issue number10
DOIs
Publication statusPublished - Oct 2014
Externally publishedYes

Keywords

  • 53BP1
  • DNA DAMAGE
  • GFP
  • MiaPaCa-2
  • NUDE MICE
  • PANCREATIC CANCER
  • REPAIR RESPONSE
  • SKIN FLAP
  • THREE-DIMENSIONAL CULTURE GELFOAM® IMAGING
  • UVB
  • UVC

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Uehara, F., Miwa, S., Tome, Y., Hiroshima, Y., Yano, S., Yamamoto, M., Efimova, E., Matsumoto, Y., Maehara, H., Bouvet, M., Kanaya, F., & Hoffman, R. M. (2014). Comparison of UVB and UVC effects on the DNA damage-response protein 53BP1 in human pancreatic cancer. Journal of Cellular Biochemistry, 115(10), 1724-1728. https://doi.org/10.1002/jcb.24837