Cysteine Protection against X Irradiation

Patt, Harvey M.; Tyree, Ella B.; Straube, Robert L.; Smith, Douglas E.

doi:10.1126/science.110.2852.213

Cited by 556 publications

(167 citation statements)

References 2 publications

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“…One of the bestrecognized concepts in radiation biology is that the presence of oxygen increases the efficacy of radiation whereas GSH is a radioprotector. In 1949, it was reported that L-cysteine, a rate limiting substrate in GSH synthesis, protected rats from lethal radiation doses [51]. This study indicated an important role for GSH in radiation biology and seeded the idea of using GSH depletion as a method to sensitize cancer cells.…”

Section: Targeting Gsh Synthesis: Key Discoveriesmentioning

confidence: 75%

Harnessing drug resistance: Using ABC transporter proteins to target cancer cells

Leitner

Kachadourian

Day

2007

Biochemical Pharmacology

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The ATP-binding cassette (ABC) class of proteins is one of the most functionally diverse transporter families found in biological systems. Although the abundance of ABC proteins varies between species, they are highly conserved in sequence and often demonstrate similar functions across prokaryotic and eukaryotic organisms. Beginning with a brief summary of the events leading to our present day knowledge of ABC transporters, the purpose of this review is to discuss the potential for utilizing ABC transporters as a means for cellular glutathione (GSH) modulation. GSH is one of the most abundant thiol antioxidants in cells. It is involved in cellular division, protein and DNA synthesis, maintenance of cellular redox status and xenobiotic metabolism. Cellular GSH levels are often altered in many disease states including cancer. Over the past two decades there has been considerable emphasis on methods to sensitize cancer cells to chemotherapeutics and ionization radiation therapy by GSH depletion. We contend that ABC transporters, particularly multi-drug resistant proteins (MRPs), may be used as therapeutic targets for applications aimed at modulation of GSH levels. This review will emphasize MRP-mediated modulation of intracellular GSH levels as a potential alternative and adjunctive approach for cancer therapy.

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Section: Targeting Gsh Synthesis: Key Discoveriesmentioning

confidence: 75%

Harnessing drug resistance: Using ABC transporter proteins to target cancer cells

Leitner

Kachadourian

Day

2007

Biochemical Pharmacology

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“…Sulfhydryl bond in the structure of l ‐cysteine ( l ‐Cys) allows it to act as a radio protector by scavenging free radicals 22, 23, 24. Experiments in rats demonstrated that animals administered l ‐Cys withstood normally lethal doses of X‐rays25 and showed considerably reduced damage to essential organs compared to untreated animals 26. In addition, cysteine‐containing polypeptides form disulfide cross‐links, which are useful in drug carrier design,27 as reduction of disulfide bonds can be used to trigger the release of anticancer drugs 28.…”

Section: Introductionmentioning

confidence: 99%

Radiation‐Sensitive Dendrimer‐Based Drug Delivery System

Chou

Yuh

et al. 2017

Advanced Science

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Combination of chemotherapy and radiotherapy is used to enhance local drug delivery while reducing off‐target tissue effects. Anticancer drug doxorubicin (DOX) is loaded into l‐cysteine modified G4.5 dendrimer (GC/DOX) and released at different pH values in the presence and absence of γ‐radiation. Presence of γ‐radiation significantly improves DOX release from the GC/DOX under acidic pH conditions, suggesting that GC dendrimer is a radiation‐sensitive drug delivery system. GC/DOX is further evaluated by determining cytotoxicity in uterine cervical carcinoma HeLa cells. GC/DOX shows high affinity for cancer cells and effective drug release following an external stimulus (radiation exposure), whereas an in vivo zebrafish study confirms that l‐cysteine acts as a radiosensitizer. GC/DOX treatment combined with radiotherapy synergistically and successfully inhibits cancer cell growth.

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“…Des études très étendues sur ce problème ont montré que des composés variés (tels des cyanures [1,2], des nitriles [1,3], des aminoacides soufrés [4,5,6], MEA, AET, MEG) fournissent dans beaucoup de cas une réelle radio protection, mais présentent aussi de sérieux inconvénients :…”

Section: -Introductionunclassified

Évaluation biochimique de la propriété radioprotectrice du « shirkhesht »

Rouhanizadeh¹,

Khalkali²

1971

Radioprotection

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RÉSUMÉDans le cadre de recherches sur l'action radioprotectrice du « Shirkhesht », substance naturelle non toxique, on a fait une évaluation biochimique du complexe DNP chez les animaux irradiés dont un lot a reçu le produit et l'autre n'en a pas reçu. La sensibilité du complexe désoxyribonucléoprotéidique (complexe DNP) à l'irradiation a fait l'objet de recherches. Les résultats obtenus confirment : -un changement considérable du complexe DNP dans les tissus irradiés, -le pouvoir radioprotecteur, digne d'attention (25-30 %), du « Shirkhesht » qui présente le grand avantage d'être utilisable par voie orale. SUMMARYIn order to investigate the radioprotective action of " Shirkhesht ", a non toxic natural substance, a biochemical evaluation of the DNP complex in irradiated ani mals has been made both with and without administration of " Shirkhesht ". The sensitivity of the DNP complex to irradiation has also been investigated. The results so far confirm : -the considerable change of the DNP complex in the irradiated tissues, -" Shirkhesht " appears to have quite a considerable radioprotective action (25-30 %) with the main advantage of being administrated orally.

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Cysteine Protection against X Irradiation

Cited by 556 publications

References 2 publications

Harnessing drug resistance: Using ABC transporter proteins to target cancer cells

Harnessing drug resistance: Using ABC transporter proteins to target cancer cells

Radiation‐Sensitive Dendrimer‐Based Drug Delivery System

Évaluation biochimique de la propriété radioprotectrice du « shirkhesht »

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