Matches in SemOpenAlex for { <https://semopenalex.org/work/W3207413441> ?p ?o ?g. }
Showing items 1 to 88 of
88
with 100 items per page.
- W3207413441 endingPage "537" @default.
- W3207413441 startingPage "537" @default.
- W3207413441 abstract "2288 The mechanisms by which the HIV protease inhibitor ritonavir inhibits cancer cell growth are poorly understood. We have previously demonstrated that ritonavir inhibits calpain and not the proteasome in the MDA-MB-231 line and that ritonavir inhibits the growth of the MDA-MB-231 line in vitro and in a mammary fat pad xenograft model. Ritonavir up-regulates the calpain target p27, and induces nuclear localization, associated with inhibition of cell cycle progression at the G1/S checkpoint. Apoptosis is induced 3-fold by ritonavir compared to the vehicle control at 24 h, from 5 to 18%, as measured by propidium iodide/Annexin-FITC staining. Akt levels are not affected at 24 of ritonavir exposure, while Akt phosphorylation is down-regulated by 80%. These results indicate that ritonavir inhibits two targets in the MDA-MB-231 line. Calpain inhibition by m-calpain siRNA or PD150606 does not inhibit Akt phosphorylation or induce apoptosis, but up-regulates p27, suggesting that ritonavir-induced apoptosis may involve a non-protease target. One candidate ritonavir target is Hsp90, which promotes Akt folding and phosphorylation. Surface plasmon resonance biosensor analysis revealed that ritonavir binds to human Hsp90, exhibiting a KD of 7.8 microM. Ritonavir inhibits Hsp90 /Akt and Hsp90/mutant p53 complex formation in the MDA-MB-231 line, suggesting that ritonavir blocks Hsp90 interaction with client proteins. These results indicate that ritonavir inhibits breast cancer growth, in part, by inhibiting Hsp90 function and associated Akt phosphorylation, resulting in apoptosis, and in part, by intracellular calpain inhibition and upregulation of p27, resulting in G1 cell cycle arrest." @default.
- W3207413441 created "2021-10-25" @default.
- W3207413441 creator A5048663075 @default.
- W3207413441 creator A5050885519 @default.
- W3207413441 creator A5055641574 @default.
- W3207413441 creator A5058946252 @default.
- W3207413441 creator A5077837457 @default.
- W3207413441 creator A5080385299 @default.
- W3207413441 date "2005-05-01" @default.
- W3207413441 modified "2023-09-24" @default.
- W3207413441 title "Ritonavir inhibits breast cancer cell proliferation, in part, by inhibiting Hsp90 function and Akt phosphorylation" @default.
- W3207413441 hasPublicationYear "2005" @default.
- W3207413441 type Work @default.
- W3207413441 sameAs 3207413441 @default.
- W3207413441 citedByCount "0" @default.
- W3207413441 crossrefType "journal-article" @default.
- W3207413441 hasAuthorship W3207413441A5048663075 @default.
- W3207413441 hasAuthorship W3207413441A5050885519 @default.
- W3207413441 hasAuthorship W3207413441A5055641574 @default.
- W3207413441 hasAuthorship W3207413441A5058946252 @default.
- W3207413441 hasAuthorship W3207413441A5077837457 @default.
- W3207413441 hasAuthorship W3207413441A5080385299 @default.
- W3207413441 hasConcept C104317684 @default.
- W3207413441 hasConcept C11960822 @default.
- W3207413441 hasConcept C142462285 @default.
- W3207413441 hasConcept C181199279 @default.
- W3207413441 hasConcept C185592680 @default.
- W3207413441 hasConcept C190283241 @default.
- W3207413441 hasConcept C203014093 @default.
- W3207413441 hasConcept C205260736 @default.
- W3207413441 hasConcept C2775932338 @default.
- W3207413441 hasConcept C2779298103 @default.
- W3207413441 hasConcept C2993143319 @default.
- W3207413441 hasConcept C3013748606 @default.
- W3207413441 hasConcept C502942594 @default.
- W3207413441 hasConcept C55493867 @default.
- W3207413441 hasConcept C56928146 @default.
- W3207413441 hasConcept C75217442 @default.
- W3207413441 hasConcept C86803240 @default.
- W3207413441 hasConcept C95444343 @default.
- W3207413441 hasConceptScore W3207413441C104317684 @default.
- W3207413441 hasConceptScore W3207413441C11960822 @default.
- W3207413441 hasConceptScore W3207413441C142462285 @default.
- W3207413441 hasConceptScore W3207413441C181199279 @default.
- W3207413441 hasConceptScore W3207413441C185592680 @default.
- W3207413441 hasConceptScore W3207413441C190283241 @default.
- W3207413441 hasConceptScore W3207413441C203014093 @default.
- W3207413441 hasConceptScore W3207413441C205260736 @default.
- W3207413441 hasConceptScore W3207413441C2775932338 @default.
- W3207413441 hasConceptScore W3207413441C2779298103 @default.
- W3207413441 hasConceptScore W3207413441C2993143319 @default.
- W3207413441 hasConceptScore W3207413441C3013748606 @default.
- W3207413441 hasConceptScore W3207413441C502942594 @default.
- W3207413441 hasConceptScore W3207413441C55493867 @default.
- W3207413441 hasConceptScore W3207413441C56928146 @default.
- W3207413441 hasConceptScore W3207413441C75217442 @default.
- W3207413441 hasConceptScore W3207413441C86803240 @default.
- W3207413441 hasConceptScore W3207413441C95444343 @default.
- W3207413441 hasLocation W32074134411 @default.
- W3207413441 hasOpenAccess W3207413441 @default.
- W3207413441 hasPrimaryLocation W32074134411 @default.
- W3207413441 hasRelatedWork W1670228593 @default.
- W3207413441 hasRelatedWork W1981824089 @default.
- W3207413441 hasRelatedWork W1993722913 @default.
- W3207413441 hasRelatedWork W2020061024 @default.
- W3207413441 hasRelatedWork W2023004351 @default.
- W3207413441 hasRelatedWork W2024842934 @default.
- W3207413441 hasRelatedWork W2056025653 @default.
- W3207413441 hasRelatedWork W2061181299 @default.
- W3207413441 hasRelatedWork W2072932844 @default.
- W3207413441 hasRelatedWork W2090396091 @default.
- W3207413441 hasRelatedWork W2097816988 @default.
- W3207413441 hasRelatedWork W2141019354 @default.
- W3207413441 hasRelatedWork W2147026669 @default.
- W3207413441 hasRelatedWork W2325001609 @default.
- W3207413441 hasRelatedWork W2330694301 @default.
- W3207413441 hasRelatedWork W2391321544 @default.
- W3207413441 hasRelatedWork W244150924 @default.
- W3207413441 hasRelatedWork W2522210953 @default.
- W3207413441 hasRelatedWork W2562688262 @default.
- W3207413441 hasRelatedWork W2805272029 @default.
- W3207413441 hasVolume "65" @default.
- W3207413441 isParatext "false" @default.
- W3207413441 isRetracted "false" @default.
- W3207413441 magId "3207413441" @default.
- W3207413441 workType "article" @default.