Umeå University's logo

umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
A new G-quadruplex-specific photosensitizer inducing genome instability in cancer cells by triggering oxidative DNA damage and impeding replication fork progression
Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.ORCID iD: 0000-0002-7815-4494
Univ Angers, CNRS, MOLTECH-ANJOU, France.
Univ Angers, CNRS, MOLTECH-ANJOU, France.
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
Show others and affiliations
2023 (English)In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 51, no 12, p. 6264-6285Article in journal (Refereed) Published
Abstract [en]

Photodynamic therapy (PDT) ideally relies on the administration, selective accumulation and photoactivation of a photosensitizer (PS) into diseased tissues. In this context, we report a new heavy-atom-free fluorescent G-quadruplex (G4) DNA-binding PS, named DBI. We reveal by fluorescence microscopy that DBI preferentially localizes in intraluminal vesicles (ILVs), precursors of exosomes, which are key components of cancer cell proliferation. Moreover, purified exosomal DNA was recognized by a G4-specific antibody, thus highlighting the presence of such G4-forming sequences in the vesicles. Despite the absence of fluorescence signal from DBI in nuclei, light-irradiated DBI-treated cells generated reactive oxygen species (ROS), triggering a 3-fold increase of nuclear G4 foci, slowing fork progression and elevated levels of both DNA base damage, 8-oxoguanine, and double-stranded DNA breaks. Consequently, DBI was found to exert significant phototoxic effects (at nanomolar scale) toward cancer cell lines and tumor organoids. Furthermore, in vivo testing reveals that photoactivation of DBI induces not only G4 formation and DNA damage but also apoptosis in zebrafish, specifically in the area where DBI had accumulated. Collectively, this approach shows significant promise for image-guided PDT.

Place, publisher, year, edition, pages
Oxford University Press, 2023. Vol. 51, no 12, p. 6264-6285
National Category
Biochemistry and Molecular Biology Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-212227DOI: 10.1093/nar/gkad365ISI: 000988008500001PubMedID: 37191066Scopus ID: 2-s2.0-85164253573OAI: oai:DiVA.org:umu-212227DiVA, id: diva2:1783438
Funder
Swedish Cancer Society, 22 2380 PjSwedish Research Council, VR-MH 2021–02468Knut and Alice Wallenberg Foundation, KAW 2021-0173Swedish Cancer Society, 21 0302 PT 01 HWenner-Gren Foundations, UPD2020-0097Swedish Cancer Society, 20 0827 PjFCancerforskningsfonden i Norrland, LP 22-2312Cancerforskningsfonden i Norrland, LP20 1024 2257Cancerforskningsfonden i Norrland, LP 21–2298Swedish Research Council, 2017-01531Swedish Society of Medicine, SLS-890521Region Västerbotten, RV-930167Sjöberg FoundationKnut and Alice Wallenberg Foundation, KAW 2015.0114Marianne and Marcus Wallenberg Foundation, MMW 2020.0189Swedish Cancer Society, 20 1339 PjFAvailable from: 2023-07-21 Created: 2023-07-21 Last updated: 2023-07-21Bibliographically approved

Open Access in DiVA

fulltext(2689 kB)169 downloads
File information
File name FULLTEXT01.pdfFile size 2689 kBChecksum SHA-512
77a0e32bab61e2a895df40374072d63372b8ebeb4d9f2165e32c538b72d45437439009fa54df70d4b2514158df9622d7815ad6206a05650773c8782147981d60
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMedScopus

Authority records

Deiana, MarcoKahsay, AbrahaPatel, Ankit KumarSengupta, PallabiObi, IkennaRodriguez-Marquez, EvaÖhlund, Danielvon Hofsten, JonasSabouri, Nasim

Search in DiVA

By author/editor
Deiana, MarcoKahsay, AbrahaPatel, Ankit KumarSengupta, PallabiObi, IkennaRodriguez-Marquez, EvaÖhlund, Danielvon Hofsten, JonasSabouri, Nasim
By organisation
Department of Medical Biochemistry and BiophysicsDepartment of Integrative Medical Biology (IMB)Wallenberg Centre for Molecular Medicine at Umeå University (WCMM)Oncology
In the same journal
Nucleic Acids Research
Biochemistry and Molecular BiologyCell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 169 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 697 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf