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Ra-223 induces clus...
Ra-223 induces clustered DNA damage and inhibits cell survival in several prostate cancer cell lines
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- Abramenkovs, Andris (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Rudbecklaboratoriet
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- Hariri, Mehran (författare)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Rudbecklaboratoriet
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- Spiegelberg, Diana, 1982- (författare)
- Uppsala universitet,Plastikkirurgi,Cancerprecisionsmedicin,Öron-, näs- och halssjukdomar,Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala SE-75185, Sweden,Rudbecklaboratoriet
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- Nilsson, Sten (författare)
- Karolinska Institutet
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- Stenerlöw, Bo (författare)
- Uppsala universitet,Cancerprecisionsmedicin,Rudbecklaboratoriet
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(creator_code:org_t)
- Elsevier, 2022
- 2022
- Engelska.
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Ingår i: Translational Oncology. - : Elsevier. - 1944-7124 .- 1936-5233. ; 26
- Relaterad länk:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- The bone-seeking radiopharmaceutical Xofigo (Radium-223 dichloride) has demonstrated both extended sur-vival and palliative effects in treatment of bone metastases in prostate cancer. The alpha-particle emitter Ra-223, targets regions undergoing active bone remodeling and strongly binds to bone hydroxyapatite (HAp). However, the toxicity mechanism and properties of Ra-223 binding to hydroxyapatite are not fully understood. By exposing 2D and 3D (spheroid) prostate cancer cell models to free and HAp-bound Ra-223 we here studied cell toxicity, apoptosis and formation and repair of DNA double-strand breaks (DSBs). The rapid binding with a high affinity of Ra-223 to bone-like HAp structures was evident (KD= 19.2 x 10-18 M) and almost no dissociation was detected within 24 h. Importantly, there was no significant uptake of Ra-223 in cells. The Ra-223 alpha-particle decay produced track-like distributions of the DNA damage response proteins 53BP1 and gamma H2AX induced high amounts of clustered DSBs in prostate cancer cells and activated DSB repair through non-homologous end-joining (NHEJ). Ra-223 inhibited growth of prostate cancer cells, independent of cell type, and induced high levels of apoptosis. In summary, we suggest the high cell killing efficacy of the Ra-223 was attributed to the clustered DNA damaged sites induced by alpha-particles.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- Prostate cancer
- DNA damage
- Ra-223
- alpha-particle
- HAp
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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