FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2807842437> ?p ?o ?g. }

• W2807842437 abstract "Zyflamend, a blend of herbal extracts, effectively inhibits tumor growth using preclinical models of castrate-resistant prostate cancer mediated in part by 5'-adenosine monophosphate-activated protein kinase (AMPK), a master energy sensor of the cell. Clinically, treatment with Zyflamend and/or metformin (activators of AMPK) had benefits in castrate-resistant prostate cancer patients who no longer responded to treatment. Two predominant upstream kinases are known to activate AMPK: liver kinase B1 (LKB1), a tumor suppressor, and calcium-calmodulin kinase kinase-2 (CaMKK2), a tumor promotor over-expressed in many cancers. The objective was to interrogate how Zyflamend activates AMPK by determining the roles of LKB1 and CaMKK2.AMPK activation was determined in CWR22Rv1 cells treated with a variety of inhibitors of LKB1 and CaMKK2 in the presence and absence of Zyflamend, and in LKB1-null HeLa cells that constitutively express CaMKK2, following transfection with wild type LKB1 or catalytically-dead mutants. Upstream regulation by Zyflamend of LKB1 and CaMKK2 was investigated targeting protein kinase C-zeta (PKCζ) and death-associated protein kinase (DAPK), respectively.Zyflamend's activation of AMPK appears to be LKB1 dependent, while simultaneously inhibiting CaMKK2 activity. Zyflamend failed to rescue the activation of AMPK in the presence of pharmacological and molecular inhibitors of LKB1, an effect not observed in the presence of inhibitors of CaMKK2. Using LKB1-null and catalytically-dead LKB1-transfected HeLa cells that constitutively express CaMKK2, ionomycin (activator of CaMKK2) increased phosphorylation of AMPK, but Zyflamend only had an effect in cells transfected with wild type LKB1. Zyflamend appears to inhibit CaMKK2 by DAPK-mediated phosphorylation of CaMKK2 at Ser511, an effect prevented by a DAPK inhibitor. Alternatively, Zyflamend mediates LKB1 activation via increased phosphorylation of PKCζ, where it induced translocation of PKCζ and LKB1 to their respective active compartments in HeLa cells following treatment. Altering the catalytic activity of LKB1 did not alter this translocation.Zyflamend's activation of AMPK is mediated by LKB1, possibly via PKCζ, but independent of CaMKK2 by a mechanism that appears to involve DAPK.Therefore, this is the first evidence that natural products simultaneously and antithetically regulate upstream kinases, known to be involved in cancer, via the activation of AMPK." @default.
• W2807842437 created "2018-06-21" @default.
• W2807842437 creator A5018621050 @default.
• W2807842437 creator A5024407405 @default.
• W2807842437 creator A5034214826 @default.
• W2807842437 creator A5052174724 @default.
• W2807842437 creator A5069035194 @default.
• W2807842437 creator A5072402605 @default.
• W2807842437 creator A5089986341 @default.
• W2807842437 date "2018-06-18" @default.
• W2807842437 modified "2023-09-29" @default.
• W2807842437 title "Concurrent regulation of LKB1 and CaMKK2 in the activation of AMPK in castrate-resistant prostate cancer by a well-defined polyherbal mixture with anticancer properties" @default.
• W2807842437 cites W110003791 @default.
• W2807842437 cites W1565773531 @default.
• W2807842437 cites W1860286105 @default.
• W2807842437 cites W1949736479 @default.
• W2807842437 cites W1968707800 @default.
• W2807842437 cites W1971414838 @default.
• W2807842437 cites W1973334810 @default.
• W2807842437 cites W1974810481 @default.
• W2807842437 cites W1978763812 @default.
• W2807842437 cites W1990287298 @default.
• W2807842437 cites W2004306793 @default.
• W2807842437 cites W2017043004 @default.
• W2807842437 cites W2018289835 @default.
• W2807842437 cites W2023657887 @default.
• W2807842437 cites W2028205542 @default.
• W2807842437 cites W2031716577 @default.
• W2807842437 cites W2035556432 @default.
• W2807842437 cites W2045259351 @default.
• W2807842437 cites W2048501945 @default.
• W2807842437 cites W2052612645 @default.
• W2807842437 cites W2060102571 @default.
• W2807842437 cites W2064965719 @default.
• W2807842437 cites W2067327098 @default.
• W2807842437 cites W2067979493 @default.
• W2807842437 cites W2070323923 @default.
• W2807842437 cites W2082762354 @default.
• W2807842437 cites W2093075113 @default.
• W2807842437 cites W2100837269 @default.
• W2807842437 cites W2102891343 @default.
• W2807842437 cites W2112609982 @default.
• W2807842437 cites W2116172687 @default.
• W2807842437 cites W2119041481 @default.
• W2807842437 cites W2123558789 @default.
• W2807842437 cites W2124644591 @default.
• W2807842437 cites W2125344123 @default.
• W2807842437 cites W2148828072 @default.
• W2807842437 cites W2149494499 @default.
• W2807842437 cites W2149845330 @default.
• W2807842437 cites W2155783894 @default.
• W2807842437 cites W2462514513 @default.
• W2807842437 cites W2522229157 @default.
• W2807842437 cites W2570618306 @default.
• W2807842437 cites W2587210054 @default.
• W2807842437 cites W2594772734 @default.
• W2807842437 cites W2604227827 @default.
• W2807842437 cites W2611922828 @default.
• W2807842437 cites W2739206176 @default.
• W2807842437 cites W2757754519 @default.
• W2807842437 cites W2772280433 @default.
• W2807842437 cites W2915478882 @default.
• W2807842437 cites W954574116 @default.
• W2807842437 doi "https://doi.org/10.1186/s12906-018-2255-0" @default.
• W2807842437 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6006779" @default.
• W2807842437 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29914450" @default.
• W2807842437 hasPublicationYear "2018" @default.
• W2807842437 type Work @default.
• W2807842437 sameAs 2807842437 @default.
• W2807842437 citedByCount "8" @default.
• W2807842437 countsByYear W28078424372020 @default.
• W2807842437 countsByYear W28078424372021 @default.
• W2807842437 countsByYear W28078424372023 @default.
• W2807842437 crossrefType "journal-article" @default.
• W2807842437 hasAuthorship W2807842437A5018621050 @default.
• W2807842437 hasAuthorship W2807842437A5024407405 @default.
• W2807842437 hasAuthorship W2807842437A5034214826 @default.
• W2807842437 hasAuthorship W2807842437A5052174724 @default.
• W2807842437 hasAuthorship W2807842437A5069035194 @default.
• W2807842437 hasAuthorship W2807842437A5072402605 @default.
• W2807842437 hasAuthorship W2807842437A5089986341 @default.
• W2807842437 hasBestOaLocation W28078424371 @default.
• W2807842437 hasConcept C184235292 @default.
• W2807842437 hasConcept C185592680 @default.
• W2807842437 hasConcept C2776780712 @default.
• W2807842437 hasConcept C2780124434 @default.
• W2807842437 hasConcept C502942594 @default.
• W2807842437 hasConcept C86803240 @default.
• W2807842437 hasConcept C95444343 @default.
• W2807842437 hasConcept C97029542 @default.
• W2807842437 hasConceptScore W2807842437C184235292 @default.
• W2807842437 hasConceptScore W2807842437C185592680 @default.
• W2807842437 hasConceptScore W2807842437C2776780712 @default.
• W2807842437 hasConceptScore W2807842437C2780124434 @default.
• W2807842437 hasConceptScore W2807842437C502942594 @default.
• W2807842437 hasConceptScore W2807842437C86803240 @default.
• W2807842437 hasConceptScore W2807842437C95444343 @default.
• W2807842437 hasConceptScore W2807842437C97029542 @default.
• W2807842437 hasFunder F4320312584 @default.
• W2807842437 hasFunder F4320332161 @default.

• next