Two New Faces of Amifostine: Protector from DNA Damage in
Normal Cells and Inhibitor of DNA Repair in Cancer Cells

J 2016

Two New Faces of Amifostine: Protector from DNA Damage in Normal Cells and Inhibitor of DNA Repair in Cancer Cells

HOFER, Michal; Martin FALK; Denisa KOMŮRKOVÁ; Iva FALKOVÁ; Alena BAČÍKOVÁ et al.

Základní údaje

Originální název

Two New Faces of Amifostine: Protector from DNA Damage in Normal Cells and Inhibitor of DNA Repair in Cancer Cells

Autoři

Vydání

Journal of Medicinal Chemistry, Washington, American Chemical Society, 2016, 0022-2623

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30104 Pharmacology and pharmacy

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 6.259

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/16:00087934

Organizační jednotka

Lékařská fakulta

DOI

https://doi.org/10.1021/acs.jmedchem.5b01628

UT WoS

000374430800010

EID Scopus

2-s2.0-84966341183

Klíčová slova anglicky

ALTERNATIVE SPLICING VARIANT; ORDER CHROMATIN-STRUCTURE; STRAND BREAK REPAIR; BONE-MARROW-CELLS; ALKALINE-PHOSPHATASE; HUMAN-LYMPHOCYTES; NORMAL-TISSUES; HISTONE H2AX; MCF-7 CELLS; GAMMA-RAYS

Štítky

EL OK

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 31. 10. 2019 11:42, Mgr. Michal Petr

Anotace

V originále

Amifostine protects normal cells from DNA damage induction by ionizing radiation or chemotherapeutics, whereas cancer cells typically remain uninfluenced. While confirming this phenomenon, we have revealed by comet assay and currently the most sensitive method of DNA double strand break (DSB) quantification (based on gamma H2AX/53BP1 high-resolution immunofluorescence microscopy) that amifostine treatment supports DSB repair in gamma-irradiated normal NHDF fibroblasts but alters it in MCF7 carcinoma cells. These effects follow from the significantly lower activity of alkaline phosphatase measured in MCF7 cells and their supernatants as compared with NHDF fibroblasts. Liquid chromatography-mass spectrometry confirmed that the amifostine conversion to WR-1065 was significantly more intensive in normal NHDF cells than in tumor MCF cells. In conclusion, due to common differences between normal and cancer cells in their abilities to convert amifostine to its active metabolite WR-1065, amifostine may not only protect in multiple ways normal cells from radiation-induced DNA damage but also make cancer cells suffer from DSB repair alteration.

Návaznosti

ED1.1.00/02.0068, projekt VaV

Název: CEITEC - central european institute of technology

GA16-01137S, projekt VaV

Název: Faktory genomové stability u mechu a vyšších rostlin

Investor: Grantová agentura ČR, Faktory genomové stability u mechu a vyšších rostlin

GA16-12454S, projekt VaV

Název: Charakterizace a modifikace komplexní odpovědi buněk nádorů hlavy a krku na různá záření - krok kupředu ke kombinované personalizované (radio)terapii

Investor: Grantová agentura ČR, Charakterizace a modifikace komplexní odpovědi buněk nádorů hlavy a krku na různá záření - krok kupředu ke kombinované personalizované (radio)terapii

GBP302/12/G157, projekt VaV

Název: Dynamika a organizace chromosomů během buněčného cyklu a při diferenciaci v normě a patologii

Investor: Grantová agentura ČR, Dynamika a organizace chromosomů během buněčného cyklu a při diferenciaci v normě a patologii

NV16-29835A, projekt VaV

Název: Molekulárně-genetické markery predikce účinnosti radioterapie u nádorů hlavy a krku

Citovat

HOFER, Michal; Martin FALK; Denisa KOMŮRKOVÁ; Iva FALKOVÁ; Alena BAČÍKOVÁ; Bořivoj KLEJDUS; Eva PAGÁČOVÁ; Lenka ŠTEFANČÍKOVÁ; Lenka WEITEROVÁ; Karel J. ANGELIS; Stanislav KOZUBEK; Ladislav DUŠEK a Štefan GALBAVÝ. Two New Faces of Amifostine: Protector from DNA Damage in Normal Cells and Inhibitor of DNA Repair in Cancer Cells. Journal of Medicinal Chemistry. Washington: American Chemical Society, 2016, roč. 59, č. 7, s. 3003-3017. ISSN 0022-2623. Dostupné z: https://doi.org/10.1021/acs.jmedchem.5b01628.

@article{1345392,
   author = {Hofer, Michal and Falk, Martin and Komůrková, Denisa and Falková, Iva and Bačíková, Alena and Klejdus, Bořivoj and Pagáčová, Eva and Štefančíková, Lenka and Weiterová, Lenka and Angelis, Karel J. and Kozubek, Stanislav and Dušek, Ladislav and Galbavý, Štefan},
   article_location = {Washington},
   article_number = {7},
   doi = {https://doi.org/10.1021/acs.jmedchem.5b01628},
   keywords = {ALTERNATIVE SPLICING VARIANT; ORDER CHROMATIN-STRUCTURE; STRAND BREAK REPAIR; BONE-MARROW-CELLS; ALKALINE-PHOSPHATASE; HUMAN-LYMPHOCYTES; NORMAL-TISSUES; HISTONE H2AX; MCF-7 CELLS; GAMMA-RAYS},
   language = {eng},
   issn = {0022-2623},
   journal = {Journal of Medicinal Chemistry},
   title = {Two New Faces of Amifostine: Protector from DNA Damage in Normal Cells and Inhibitor of DNA Repair in Cancer Cells},
   volume = {59},
   year = {2016}
}

TY  - JOUR
ID  - 1345392
AU  - Hofer, Michal - Falk, Martin - Komůrková, Denisa - Falková, Iva - Bačíková, Alena - Klejdus, Bořivoj - Pagáčová, Eva - Štefančíková, Lenka - Weiterová, Lenka - Angelis, Karel J. - Kozubek, Stanislav - Dušek, Ladislav - Galbavý, Štefan
PY  - 2016
TI  - Two New Faces of Amifostine: Protector from DNA Damage in Normal Cells and Inhibitor of DNA Repair in Cancer Cells
JF  - Journal of Medicinal Chemistry
VL  - 59
IS  - 7
SP  - 3003-3017
EP  - 3003-3017
PB  - American Chemical Society
SN  - 00222623
KW  - ALTERNATIVE SPLICING VARIANT
KW  - ORDER CHROMATIN-STRUCTURE
KW  - STRAND BREAK REPAIR
KW  - BONE-MARROW-CELLS
KW  - ALKALINE-PHOSPHATASE
KW  - HUMAN-LYMPHOCYTES
KW  - NORMAL-TISSUES
KW  - HISTONE H2AX
KW  - MCF-7 CELLS
KW  - GAMMA-RAYS
N2  - Amifostine protects normal cells from DNA damage induction by ionizing radiation or chemotherapeutics, whereas cancer cells typically remain uninfluenced. While confirming this phenomenon, we have revealed by comet assay and currently the most sensitive method of DNA double strand break (DSB) quantification (based on gamma H2AX/53BP1 high-resolution immunofluorescence microscopy) that amifostine treatment supports DSB repair in gamma-irradiated normal NHDF fibroblasts but alters it in MCF7 carcinoma cells. These effects follow from the significantly lower activity of alkaline phosphatase measured in MCF7 cells and their supernatants as compared with NHDF fibroblasts. Liquid chromatography-mass spectrometry confirmed that the amifostine conversion to WR-1065 was significantly more intensive in normal NHDF cells than in tumor MCF cells. In conclusion, due to common differences between normal and cancer cells in their abilities to convert amifostine to its active metabolite WR-1065, amifostine may not only protect in multiple ways normal cells from radiation-induced DNA damage but also make cancer cells suffer from DSB repair alteration.
ER  -

HOFER, Michal; Martin FALK; Denisa KOMŮRKOVÁ; Iva FALKOVÁ; Alena BAČÍKOVÁ; Bořivoj KLEJDUS; Eva PAGÁČOVÁ; Lenka ŠTEFANČÍKOVÁ; Lenka WEITEROVÁ; Karel J. ANGELIS; Stanislav KOZUBEK; Ladislav DUŠEK a Štefan GALBAVÝ. Two New Faces of Amifostine: Protector from DNA Damage in Normal Cells and Inhibitor of DNA Repair in Cancer Cells. \textit{Journal of Medicinal Chemistry}. Washington: American Chemical Society, 2016, roč.~59, č.~7, s.~3003-3017. ISSN~0022-2623. Dostupné z: https://doi.org/10.1021/acs.jmedchem.5b01628.

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