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
Protoporphyrin IX is a dual inhibitor of p53/MDM2 and p53/MDM4 interactions and induces apoptosis in B-cell chronic lymphocytic leukemia cells
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Solnavagen 9, S-17165 Stockholm, Sweden;Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Pathol Ctr, Sch Med, 100 Haining Rd, Shanghai 200080, Peoples R China.
Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Solnavagen 9, S-17165 Stockholm, Sweden.ORCID iD: 0000-0002-1768-3544
Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Solnavagen 9, S-17165 Stockholm, Sweden.
Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Solnavagen 9, S-17165 Stockholm, Sweden.
2019 (English)In: CELL DEATH DISCOVERY, ISSN 2058-7716, Vol. 5, article id 77Article in journal (Refereed) Published
Abstract [en]

p53 is a tumor suppressor, which belongs to the p53 family of proteins. The family consists of p53, p63 and p73 proteins, which share similar structure and function. Activation of wild-type p53 or TAp73 in tumors leads to tumor regression, and small molecules restoring the p53 pathway are in clinical development. Protoporphyrin IX (PpIX), a metabolite of aminolevulinic acid, is a clinically approved drug applied in photodynamic diagnosis and therapy. PpIX induces p53-dependent and TAp73-dependent apoptosis and inhibits TAp73/MDM2 and TAp73/MDM4 interactions. Here we demonstrate that PpIX is a dual inhibitor of p53/MDM2 and p53/MDM4 interactions and activates apoptosis in B-cell chronic lymphocytic leukemia cells without illumination and without affecting normal cells. PpIX stabilizes p53 and TAp73 proteins, induces p53-downstream apoptotic targets and provokes cancer cell death at doses non-toxic to normal cells. Our findings open up new opportunities for repurposing PpIX for treating lymphoblastic leukemia with wild-type TP53.

Place, publisher, year, edition, pages
Nature Publishing Group, 2019. Vol. 5, article id 77
National Category
Cancer and Oncology Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-382461DOI: 10.1038/s41420-019-0157-7ISI: 000463095400003PubMedID: 30886745OAI: oai:DiVA.org:uu-382461DiVA, id: diva2:1313783
Available from: 2019-05-06 Created: 2019-05-06 Last updated: 2019-05-06Bibliographically approved

Open Access in DiVA

fulltext(1017 kB)37 downloads
File information
File name FULLTEXT01.pdfFile size 1017 kBChecksum SHA-512
5d7502966dbcaf5dfdf632dfe574f4ccc3b77447e5933411e46fa2c912add9d1ef517f1f613fea4a8555598995c380308618a9105cb801b65df232205b1242c4
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Malik, Natasha
By organisation
Department of Immunology, Genetics and Pathology
Cancer and OncologyCell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
Total: 37 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: 291 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