Bosnian
Albanian
Arabic
Armenian
Azerbaijani
Belarusian
Bengali
Bosnian
Catalan
Czech
Danish
Deutsch
Dutch
English
Estonian
Finnish
Français
Greek
Haitian Creole
Hebrew
Hindi
Hungarian
Icelandic
Indonesian
Irish
Italian
Japanese
Korean
Latvian
Lithuanian
Macedonian
Mongolian
Norwegian
Persian
Polish
Portuguese
Romanian
Russian
Serbian
Slovak
Slovenian
Spanish
Swahili
Swedish
Turkish
Ukrainian
Vietnamese
Български
中文(简体)
中文(繁體)
Journal of Biological Chemistry 2013-Nov

Targeting aberrant glutathione metabolism to eradicate human acute myelogenous leukemia cells.

Samo registrirani korisnici mogu prevoditi članke
Prijavite se / prijavite se
Veza se sprema u međuspremnik
Shanshan Pei
Mohammad Minhajuddin
Kevin P Callahan
Marlene Balys
John M Ashton
Sarah J Neering
Eleni D Lagadinou
Cheryl Corbett
Haobin Ye
Jane L Liesveld

Ključne riječi

Sažetak

The development of strategies to eradicate primary human acute myelogenous leukemia (AML) cells is a major challenge to the leukemia research field. In particular, primitive leukemia cells, often termed leukemia stem cells, are typically refractory to many forms of therapy. To investigate improved strategies for targeting of human AML cells we compared the molecular mechanisms regulating oxidative state in primitive (CD34(+)) leukemic versus normal specimens. Our data indicate that CD34(+) AML cells have elevated expression of multiple glutathione pathway regulatory proteins, presumably as a mechanism to compensate for increased oxidative stress in leukemic cells. Consistent with this observation, CD34(+) AML cells have lower levels of reduced glutathione and increased levels of oxidized glutathione compared with normal CD34(+) cells. These findings led us to hypothesize that AML cells will be hypersensitive to inhibition of glutathione metabolism. To test this premise, we identified compounds such as parthenolide (PTL) or piperlongumine that induce almost complete glutathione depletion and severe cell death in CD34(+) AML cells. Importantly, these compounds only induce limited and transient glutathione depletion as well as significantly less toxicity in normal CD34(+) cells. We further determined that PTL perturbs glutathione homeostasis by a multifactorial mechanism, which includes inhibiting key glutathione metabolic enzymes (GCLC and GPX1), as well as direct depletion of glutathione. These findings demonstrate that primitive leukemia cells are uniquely sensitive to agents that target aberrant glutathione metabolism, an intrinsic property of primary human AML cells.

Pridružite se našoj
facebook stranici

Najkompletnija baza ljekovitog bilja potpomognuta naukom

  • Radi na 55 jezika
  • Biljni lijekovi potpomognuti naukom
  • Prepoznavanje biljaka po slici
  • Interaktivna GPS karta - označite bilje na lokaciji (uskoro)
  • Pročitajte naučne publikacije povezane sa vašom pretragom
  • Pretražite ljekovito bilje po učincima
  • Organizirajte svoja interesovanja i budite u toku sa istraživanjem vijesti, kliničkim ispitivanjima i patentima

Upišite simptom ili bolest i pročitajte o biljkama koje bi mogle pomoći, unesite travu i pogledajte bolesti i simptome protiv kojih se koristi.
* Sve informacije temelje se na objavljenim naučnim istraživanjima

Google Play badgeApp Store badge